-cloud properties over the period July 1983 to August 1994 suggests that lowclouds are statistically related to two processes, (1) GCR and (2) El Nino-Southern Oscillation (ENSO), with GCR explaining a greater percentage of the total variance. Areas where satellites have an unobstructed view of lowcloud possess...

[1] The recently reported correlation between clouds and galactic cosmic rays (GCR) implies the existence of a previously unknown process linking solar variability and climate. An analysis of the interannual variability of International Satellite Cloud Climatology Project D2 (ISCCP-D2) low....... Instead, it is argued that a mechanism involving solar variability via GCR ionization of the atmosphere is consistent with these results. However, the results are marginal when including the recently extended ISCCP-D2 data covering the period until September 2001. This, we believe, is related to problems...

The influence of solar variability on climate is currently uncertain. Recent observations have indicated a possible mechanism via the influence of solar modulated cosmic rays on global cloud cover. Here we show that the influence of solar variability is strongest in lowclouds (<= 3.2km). These are liquid water clouds which points to a microphysical mechanism involving enhanced aerosol formation. If confirmed it suggests that the average state of the Heliosphere is important for climate on Earth. The estimated response in lowclouds due to a doubling of solar activity is a 1.4 W/m2 warming.

The influence of solar variability on climate is currently uncertain. Recent observations have indicated a possible mechanism via the influence of solar modulated cosmic rays on global cloud cover. Surprisingly the influence of solar variability is strongest in lowclouds (less than or equal to3 ......), which points to a microphysical mechanism involving aerosol formation that is enhanced by ionization due to cosmic rays. If confirmed it suggests that the average state of the heliosphere is important for climate on Earth.......The influence of solar variability on climate is currently uncertain. Recent observations have indicated a possible mechanism via the influence of solar modulated cosmic rays on global cloud cover. Surprisingly the influence of solar variability is strongest in lowclouds (less than or equal to3 km...

The Arctic is one of the most climatically sensitive regions of the Earth. Climate models robustly project the Arctic to warm 2-3 times faster than the global mean surface temperature, termed polar warming amplification (PWA), but also display the widest range of surface temperature projections in this region. The response of the Arctic to increased CO2 modulates the response in tropical and extra-tropical regions through teleconnections in the atmospheric circulation. An increased frequency of extreme precipitation events in the northern mid-latitudes, for example, has been linked to the change in the background equator-to-pole temperature gradient implied by PWA. Understanding the Arctic climate system is therefore important for predicting global climate change. The ice albedo feedback is the primary mechanism driving PWA, however cloud and dynamical feedbacks significantly contribute. These feedback mechanisms, however, do not operate independently. How do clouds respond to variations in sea ice? This critical question is addressed by combining sea ice, cloud, and radiation observations from satellites, including CERES, CloudSAT, CALIPSO, MODIS, and microwave radiometers, to investigate sea ice-cloud interactions at the interannual timescale in the Arctic. Cloud characteristics are strongly tied to the atmospheric dynamic and thermodynamic state. Therefore, the sensitivity of Arctic cloud characteristics, vertical distribution and optical properties, to sea ice anomalies is computed within atmospheric dynamic and thermodynamic regimes. Results indicate that the cloud response to changes in sea ice concentration differs significantly between atmospheric state regimes. This suggests that (1) the atmospheric dynamic and thermodynamic characteristics and (2) the characteristics of the marginal ice zone are important for determining the seasonal forcing by cloud on sea ice variability.

The objective of this work is to determine the baseline impact properties of vanadium-base alloys as a function of compositional variables. Up-to-date results on impact properties of unirradiated V, V-Ti, V-Cr-Ti and V-Ti-Si alloys are presented and reviewed in this paper, with an emphasis on the most promising class of alloys, i.e., V-(4-5)Cr-(3-5)Ti containing 400-1000 wppm Si. Database on impact energy and ductile-brittle transition temperature (DBTT) has been established from Charpy impact tests on small laboratory as well as production-scale heats. DBTT is influenced most significantly by Cr contents and, to a lesser extent, by Ti contents of the alloys. When combined contents of Cr and Ti were {le}10 wt.%, V-Cr-Ti alloys exhibit excellent impact properties, i.e., DBTTproperties of the production-scale heat of the U.S. reference alloy V-4Cr- 4Ti were as good as those of the laboratory-scale heats. Optimal impact properties of the reference alloy were obtained after annealing the as-rolled products at 1000{degrees}C-1050{degrees}C for 1-2 h in high-quality vacuum. 17 refs., 6 figs., 2 tabs.

A significant correlation between the annual cosmic ray flux and the amount of lowclouds has recently been found for the past 20 years. However, of the physical explanations suggested, none has been quantitatively verified in the atmosphere by a combination of modelling and experiment. Here we...... study the relation between the global distributions of the observed lowcloud amount and the calculated tropospheric ionization induced by cosmic rays. We find that the time evolution of the lowcloud amount can be decomposed into a long-term trend and inter-annual variations, the latter depicting...... dependence gives strong support for the hypothesis that the cosmic ray induced ionization modulates cloud properties....

Background: Dopamine D-2/3 receptor (D2/3R) agonist radiopharmaceuticals are considered superior to antagonists to detect dopamine release, e.g. induced by amphetamines. Agonists bind preferentially to the high-affinity state of the dopamine D2R, which has been proposed as the reason why agonists ar

The fluorescence and laser properties of ten aromatic compounds, specially chosen from the p-oligophenylenes (D(2) symmetry) or m-oligophenylenes (C(2) or D(3) symmetry) are studied experimentally (at 293 K) and quantum chemically. The quantum yields, gamma and the decay times, tau(f) of fluorescence are measured for deaerated and non-deaerated cyclohexane solutions. The oscillator strengths, f(e) of the S(0)-->S(p) (1A-->(1)L(a)) and S(0)-->S(alpha) (1A-->(1)L(b)) transitions, fluorescence, k(f) and intersystem crossing, k(ST), rate constants, and natural lifetimes, tau(0)(T) are calculated. The lowest 1L(b), 1L(a) and 3L(b) (77 K) levels are determined. It is found that all p-oligophenylenes from p-terphenyl onwards are excellent, photochemically stable laser dyes although the solubility in this series decreases dramatically. On the basis of trends observed in p-oligophenylenes (D(2)-series) and on the properties of the experimentally studied m-oligophenylenes of the C(2)- and D(3)-series, the fluorescence and laser properties of other compounds from these series are estimated/predicted. It is shown, for the first time, that m-oligophenylenes of the C(2)-series, from 1,3-di(p-terphenyl)benzene will acquire fluorescence of 1L(a)-->(1)A nature and could be extremely effective laser dyes. It is also shown that m-oligophenylenes of the D(3)-series, from 1,3,5-tri(p-quaterphenyl)benzene will also acquire 1L(a)-->(1)A nature fluorescence and laser ability, although this would not be as good as that of compounds in the C(2)-series. It is concluded that m-oligophenylenes can be used not only for passive mode locking but some may also be used as laser dyes and scintillators. The results obtained are important for various practical purposes and theoretical considerations.

Blonanserin is a novel antipsychotic agent that preferentially interacts with dopamine D(2) and 5-HT(2A) receptors. To assess the atypical properties of blonanserin, we evaluated its propensity to induce extrapyramidal side effects (EPS) and to enhance forebrain Fos expression in mice. The actions of AD-6048, a primary metabolite of blonanserin, in modulating haloperidol-induced EPS were also examined. Blonanserin (0.3-10mg/kg, p.o.) did not significantly alter the pole-descending behavior of mice in the pole test or increase the catalepsy time, while haloperidol (0.3-3mg/kg, p.o.) caused pronounced bradykinesia and catalepsy. Blonanserin and haloperidol at the above doses significantly enhanced Fos expression in the shell (AcS) region of the nucleus accumbens and dorsolateral striatum (dlST). The extent of blonanserin-induced Fos expression in the AcS was comparable to that induced by haloperidol. However, the striatal Fos expression by blonanserin was less prominent as compared to haloperidol. Furthermore, combined treatment of AD-6048 (0.1-3mg/kg, s.c.) with haloperidol (0.5mg/kg, i.p.) significantly attenuated haloperidol-induced bradykinesia and catalepsy. The present results show that blonanserin behaves as an atypical antipsychotic both in inducing EPS and enhancing forebrain Fos expression. In addition, AD-6048 seems to contribute at least partly to the atypical properties of blonanserin. Copyright 2010 Elsevier Inc. All rights reserved.

Marine lowclouds are a major determinant of the Earth?s albedo and are a major source of uncertainty in how the climate responds to changing greenhouse gas levels and anthropogenic aerosol. Marine lowclouds are particularly difficult to simulate accurately in climate models, and their remote locations present a significant observational challenge. A complex set of interacting controlling processes determine the coverage, condensate loading, and microphysical and radiative properties of marine lowclouds. Marine lowclouds are sensitive to atmospheric aerosol in several ways. Interactions at microphysical scales involve changes in the concentration of cloud droplets and precipitation, which induce cloud dynamical impacts including changes in entrainment and mesoscale organization. Marine lowclouds are also impacted by atmospheric heating changes due to absorbing aerosols. The response of marine lowclouds to aerosol perturbations depends strongly upon the unperturbed aerosol-cloud state, which necessitates greater understanding of processes controlling the budget of aerosol in the marine boundary layer. Entrainment and precipitation mediate the response of lowclouds to aerosols but these processes also play leading roles in controlling the aerosol budget. The U.S. Department of Energy Atmospheric Radiation Measurement (ARM) Climate Research Facility and Atmospheric System Research (ASR) program are making major recent investments in observational data sets from fixed and mobile sites dominated by marine lowclouds. This report provides specific action items for how these measurements can be used together with process modeling to make progress on understanding and quantifying the key cloud and aerosol controlling processes in the next 5-10 years. Measurements of aerosol composition and its variation with particle size are needed to advance a quantitative, process-level understanding of marine boundary-layer aerosol budget. Quantitative precipitation estimates

Based on liquid variational perturbation theory with quantum mechanics correction, the effective exp-6 potential is adopted to compute the shock Hugoniot of liquid H2+D2 mixtures at different molar rations. An examination of the confidence of the above computation is performed by comparing experiments and calculations, in which similar calculation procedure used for H2+D2 is adopted for H2 and D2 each, since no experimental data are available to conduct this kind of comparison. Good agreement in both comparisons is found. This fact may look as if an indirect positive verification of calculation procedure was used here at least in the pressure and temperature domain covered by the experimental data of H2 and D2 used for comparison, numerically nearly up to 20 GPa and 104 K.

In present paper, we report the production and detailed structural analysis of deuterium-enriched rye grass (Lolium multiflorum) for neutron scattering experiments. An efficient method to produce deuterated biomass was developed by designing hydroponic perfusion chambers. In preliminary studies, the partial deuterated rye samples were grown in increasing levels of D2O to study the seed germination and the level of deuterium incorporation as a function of D2O concentration. Solution NMR method indicated 36.9 % deuterium incorporation in 50 % D2O grown annual rye samples and further significant increase in the deuterium incorporation level was observed by germinating the rye seedlings in H2O and growing in 50 % D2O inside the perfusion chambers. Moreover, in an effort to compare the substrate characteristics related to enzymatic hydrolysis on deuterated and protiated version of biomass, annual rye grown in 50 % D2O was selected for detailed biomass characterization studies. The compositional analyses, degree of polymerization and cellulose crystallinity were compared with its protiated control. The cellulose molecular weight indicated slight variation with deuteration; however, hemicellulose molecular weights and cellulose crystallinity remain unaffected with the deuteration. Besides the minor differences in biomass components, the development of deuterated biomass for neutron scattering application is essential to understand the complex biomass conversion processes.

Macrophysical properties of optically thin marine lowclouds over the nonpolar oceans (60 deg S-60 deg N) are measured using 2 years of full-resolution nighttime data from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP). Optically thin clouds, defined as the subset of marine lowclouds that do not fully attenuate the lidar signal, comprise almost half of the lowclouds over the marine domain. Regionally, the fraction of lowclouds that are optically thin (f(sub thin,cld)) exhibits a strong inverse relationship with the low-cloud cover, with maxima in the tropical trades (f(sub thin,cld) greater than 0.8) and minima in regions of persistent marine stratocumulus and in midlatitudes (f(sub thin,cld) less than 0.3). Domain-wide, a power law fit describes the cloud length distribution, with exponent beta = 2.03 +/- 0.06 (+/-95% confidence interval). On average, the fraction of a cloud that is optically thin decreases from approximately 1 for clouds smaller than 2 km to less than 0.3 for clouds larger than 30 km. This relationship is found to be independent of region, so that geographical variations in the cloud length distribution explain three quarters of the variance in f(sub thin,cld). Comparing collocated trade cumulus observations from CALIOP and the airborne High Spectral Resolution Lidar reveals that clouds with lengths smaller than are resolvable with CALIOP contribute approximately half of the lowclouds in the region sampled. A bounded cascade model is constructed to match the observations from the trades. The model shows that the observed optically thin cloud behavior is consistent with a power law scaling of cloud optical depth and suggests that most optically thin clouds only partially fill the CALIOP footprint.

Macrophysical properties of optically thin marine lowclouds over the nonpolar oceans (60 deg S-60 deg N) are measured using 2 years of full-resolution nighttime data from the Cloud-Aerosol Lidar with Orthogonal Polarization (CALIOP). Optically thin clouds, defined as the subset of marine lowclouds that do not fully attenuate the lidar signal, comprise almost half of the lowclouds over the marine domain. Regionally, the fraction of lowclouds that are optically thin (f(sub thin,cld)) exhibits a strong inverse relationship with the low-cloud cover, with maxima in the tropical trades (f(sub thin,cld) greater than 0.8) and minima in regions of persistent marine stratocumulus and in midlatitudes (f(sub thin,cld) less than 0.3). Domain-wide, a power law fit describes the cloud length distribution, with exponent beta = 2.03 +/- 0.06 (+/-95% confidence interval). On average, the fraction of a cloud that is optically thin decreases from approximately 1 for clouds smaller than 2 km to less than 0.3 for clouds larger than 30 km. This relationship is found to be independent of region, so that geographical variations in the cloud length distribution explain three quarters of the variance in f(sub thin,cld). Comparing collocated trade cumulus observations from CALIOP and the airborne High Spectral Resolution Lidar reveals that clouds with lengths smaller than are resolvable with CALIOP contribute approximately half of the lowclouds in the region sampled. A bounded cascade model is constructed to match the observations from the trades. The model shows that the observed optically thin cloud behavior is consistent with a power law scaling of cloud optical depth and suggests that most optically thin clouds only partially fill the CALIOP footprint.

Dopamine is an important neurotransmitter in the central nervous system of vertebrates and invertebrates. Despite their evolutionary distance, striking parallels exist between deuterostomian and protostomian dopaminergic systems. In both, signalling is achieved via a complement of functionally distinct dopamine receptors. In this study, we investigated the sequence, pharmacology and tissue distribution of a D2-like dopamine receptor from the red flour beetle Tribolium castaneum (TricaDop3) and compared it with related G protein-coupled receptors in other invertebrate species. The TricaDop3 receptor-encoding cDNA shows considerable sequence similarity with members of the Dop3 receptor class. Real time qRT-PCR showed high expression in both the central brain and the optic lobes, consistent with the role of dopamine as neurotransmitter. Activation of TricaDop3 expressed in mammalian cells increased intracellular Ca(2+) signalling and decreased NKH-477 (a forskolin analogue)-stimulated cyclic AMP levels in a dose-dependent manner. We studied the pharmacological profile of the TricaDop3 receptor and demonstrated that the synthetic vertebrate dopamine receptor agonists, 2 - amino- 6,7 - dihydroxy - 1,2,3,4 - tetrahydronaphthalene hydrobromide (6,7-ADTN) and bromocriptine acted as agonists. Methysergide was the most potent of the antagonists tested and showed competitive inhibition in the presence of dopamine. This study offers important information on the Dop3 receptor from Tribolium castaneum that will facilitate functional analyses of dopamine receptors in insects and other invertebrates.

The microstructure and mechanical properties of AISI D2 tool steel with up to 1.5 wt% niobium additions were investigated. The microstructural evolutions were characterized by means of optical microscopy and scanning electron microscopy techniques. Mechanical properties of the samples were measured using tensile testing, hardness measurements and Charpy impact test. The results indicated that modification of the microstructure was effectively achieved through the addition of 1.5 wt% of niobium, which refined the prior-austenite grains and decreased the volume fraction of eutectic carbides. Also, the eutectic carbide network tended to break thereby forming blocky and ribbon-like morphologies in the eutectic structures. The ductility and impact toughness of the niobium-contained steels were increased considerably and reached to about 5.8% and 15 J/cm{sup 2}, respectively. Generally, the results of this study suggest that niobium can be used as an alloying element to significantly enhance the ductility and impact toughness of D2 tool steel without affecting the hardness.

Full Text Available The electrical discharge machining (EDM process is used for generating accurate internal profiles in hardened materials. An powder additive in the hydrocarbon dielectric affects the energy distribution and sparking efficiency, and consequently the surface finish and micro-hardness. In this paper the Taguchi approach has been used to optimize and compare the surface properties in manganese powder-mixed EDM of oil-hardening non-shrinkable (OHNS and high-carbon high-chromium (D2 die steels. The results of the study show an improvement of 73% and 71.6% in the micro-hardness of OHNS and D2 die steels, respectively. The machining parameters for the best value of micro-hardness are found to be the same for both work materials. A scanning electron microscopy and X-ray diffraction analysis of the machined surfaces show a transfer of manganese and carbon from the plasma channel in the form of manganese carbide. The chemical composition of the machined surface has been further checked on an optical emission spectrometer to verify and quantify the results.

The radiation field over a broken stratocumulus cloud deck is simulated by the Monte Carlo method. We conducted four experiments to investigate the main factor for the observed shortwave reflectively over the FIRE flight 2 leg 5, in which reflectivity decreases almost linearly from the cloud center to cloud edge while the cloud top height and the brightness temperature remain almost constant through out the clouds. From our results, the geometry effect, however, did not contribute significantly to what has been observed. We found that the variation of the volume extinction coefficient as a function of its relative position in the cloud affects the reflectivity efficiently. Additional check of the brightness temperature of each experiment also confirms this conclusion. The cloud microphysical data showed some interesting features. We found that the cloud droplet spectrum is nearly log-normal distributed when the clouds were solid. However, whether the shift of cloud droplet spectrum toward the larger end is not certain. The decrease of number density from cloud center to cloud edges seems to have more significant effects on the optical properties.

We report the hydrostatic compression studies of the β-polymorph of a cyclotetramethylene tetranitramine (HMX) energetic molecular crystal using DFT-D2, a first-principles calculation based on density functional theory (DFT) with van der Waals (vdW) corrections. The molecular structure, mechanical properties, electronic properties, and equations of state of β-HMX are investigated. For the first time, we predict the elastic constants of β-HMX using DFT-D2 studies. The equations of state under hydrostatic compression are studied for pressures up to 100 GPa. We found that the N-N bonds along the minor axis are responsible for the sensitivity of β-HMX. The analysis of the charge distribution shows that the electronic charge is transferred from hydrogen atoms to nitro groups with the amount of 0.131 and 0.064e for the nitro groups along the minor axis and major axis, respectively, when pressure changes from 0 GPa to 100 GPa. The electronic energy band gap changes from direct at a pressure of 0 GPa to indirect at a pressure of 50 GPa and higher. The band gap decreases with respect to an increase in pressure, implying that the impact sensitivity increases with compression. Our study suggests that the van der Waals interactions are critically important in modeling the mechanical properties of this molecular crystal.

Starting from maximally supersymmetric (2+1)d Yang-Mills theory and using a duality transformation due to de Wit, Nicolai and Samtleben, we obtain the ghost-free Lorentzian 3-algebra theory that has recently been proposed to describe M2-branes. Our derivation does not invoke any properties of 3-algebras. Being derivable from SYM, the final theory is manifestly equivalent to it on-shell and should not be thought of as the IR limit that describes M2-branes, though it does have enhanced R-symmetry as well as superconformal symmetry off-shell.

Starting from maximally supersymmetric (2+1)d Yang-Mills theory and using a duality transformation due to de Wit, Nicolai and Samtleben, we obtain the ghost-free Lorentzian 3-algebra theory that has recently been proposed to describe M2-branes. Our derivation does not invoke any properties of 3-algebras. Being derivable from SYM, the final theory is manifestly equivalent to it on-shell and should not be thought of as the IR limit that describes M2-branes, though it does have enhanced R-symmetry as well as superconformal symmetry off-shell.

We previously reported on the synthesis of substituted phenyl-4-hydroxy-1-piperidyl indole analogues with nanomolar affinity at D2 dopamine receptors, ranging from 10- to 100-fold selective for D2 compared to the D3 dopamine receptor subtype. More recently, we evaluated a panel of aripiprazole analogues, identifying several analogues that also exhibit D2 vs D3 dopamine receptor binding selectivity. These studies further characterize the intrinsic efficacy of the compound with the greatest binding selectivity from each chemical class, 1-((5-methoxy-1H-indol-3-yl)methyl)-4-(4-(methylthio)phenyl)piperidin-4-ol (SV 293) and 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one (SV-III-130s), using an adenylyl cyclase inhibition assay, a G-protein-coupled inward-rectifying potassium (GIRK) channel activation assay, and a cell based phospho-MAPK (pERK1/2) assay. SV 293 was found to be a neutral antagonist at D2 dopamine receptors using all three assays. SV-III-130s is a partial agonist using an adenylyl cyclase inhibition assay but an antagonist in the GIRK and phospho ERK1/2 assays. To define the molecular basis for the binding selectivity, the affinity of these two compounds was evaluated using (a) wild type human D2 and D3 receptors and (b) a panel of chimeric D2/D3 dopamine receptors. Computer-assisted modeling techniques were used to dock these compounds to the human D2 and D3 dopamine receptor subtypes. It is hoped that these studies on D2 receptor selective ligands will be useful in the future design of (a) receptor selective ligands used to define the function of D2-like receptor subtypes, (b) novel pharmacotherapeutic agents, and/or (c) in vitro and in vivo imaging agents. PMID:23259040

The rotationally resolved infrared spectrum of the B+-D2 ion-neutral complex is recorded in the D-D stretch vibration region (2805-2875 cm-1) by detecting B+ photofragments. Analysis of the spectrum confirms a T-shaped equilibrium geometry for the B+-D2 complex with a vibrationally averaged intermolecular bond length of 2.247 Å, around 0.02 Å shorter than for the previously characterised B+-H2 complex [V. Dryza, B. L. J. Poad, and E. J. Bieske, J. Am. Chem. Soc. 130, 12986 (2008), 10.1021/ja8018302]. The D-D stretch band centre occurs at 2839.76 ± 0.10 cm-1, representing a -153.8 cm-1 shift from the Q1(0) transition of the free D2 molecule. A new three dimensional ab initio potential energy surface for the B++H2 interaction is calculated using the coupled cluster RCCSD(T) method and is used in variational calculations for the rovibrational energies of B+-H2 and B+-D2. The calculations predict dissociation energies of 1254 cm-1 for B+-H2 with respect to the B++H2 (j = 0) limit, and 1313 cm-1 for B+-D2 with respect to the B++D2 (j = 0) limit. The theoretical approach reproduces the rotational and centrifugal constants of the B+-H2 and B+-D2 complexes to within 3%, and the magnitude of the contraction of the intermolecular bond accompanying excitation of the H2 or D2 sub-unit, but underestimates the H-H and D-D vibrational band shifts by 7%-8%. Combining the theoretical and experimental results allows a new, more accurate estimation for the B+-H2 band origin (3939.64 ± 0.10 cm-1).

How tropical lowclouds change with climate remains the dominant source of uncertainty in global warming projections. An analysis of an ensemble of CMIP5 climate models reveals that a significant part of the spread in the models' climate sensitivity can be accounted by differences in the climatological shallowness of tropical lowclouds in weak-subsidence regimes: models with shallower lowclouds in weak-subsidence regimes tend to have a higher climate sensitivity than models with deeper lowclouds. The dynamical mechanisms responsible for the model differences are analyzed. Competing effects of parameterized boundary-layer turbulence and shallow convection are found to be essential. Boundary-layer turbulence and shallow convection are typically represented by distinct parameterization schemes in current models—parameterization schemes that often produce opposing effects on lowclouds. Convective drying of the boundary layer tends to deepen lowclouds and reduce the cloud fraction at the lowest levels; turbulent moistening tends to make lowclouds more shallow but affects the low-cloud fraction less. The relative importance different models assign to these opposing mechanisms contributes to the spread of the climatological shallowness of lowclouds and thus to the spread of low-cloud changes under global warming.

Full Text Available In this study, we examine marine lowcloud cover variability in the Southeast Pacific and its association with lower-tropospheric stability (LTS across a spectrum of timescales. On both daily and interannual timescales, LTS and lowcloud amount are very well correlated in austral summer (DJF. Meanwhile in winter (JJA, when ambient LTS increases, the LTS–lowcloud relationship substantially weakens. The DJF LTS–lowcloud relationship also weakens in years with unusually large ambient LTS values. These are generally strong El Niño years, in which DJF LTS values are comparable to those typically found in JJA. Thus the LTS–lowcloud relationship is strongly modulated by the seasonal cycle and the ENSO phenomenon. We also investigate the origin of LTS anomalies closely associated with lowcloud variability during austral summer. We find that the ocean and atmosphere are independently involved in generating anomalies in LTS and hence variability in the Southeast Pacific lowcloud deck. This highlights the importance of the physical (as opposed to chemical component of the climate system in generating internal variability in lowcloud cover. It also illustrates the coupled nature of the climate system in this region, and raises the possibility of cloud feedbacks related to LTS. We conclude by addressing the implications of the LTS–lowcloud relationship in the Southeast Pacific for lowcloud feedbacks in anthropogenic climate change.

In this work, the wear test of uncoated and chromium nitride coated AISI D2 cold work tool steel against alumina ball realized at 0.1 m/s sliding speeds and under the loads of 2.5N, 5N and 10N. Steel samples were nitrided at 575°C for 8 h in the first step of the coating process, and then chromium nitride coating was performed thermo-reactive deposition technique (TRD) in a powder mixture consisting of ferro-chromium, ammonium chloride and alumina at 1000°C for 2 h. Nitro-chromized samples were characterized by X-Ray diffraction analysis (XRD), scanning electron microscopy (SEM), micro-hardness and ball on disk wear tests. The coating layer formed on the AISI D2 steel was compact and homogeneous. X-ray studies showed that the phase formed in the coated layer is Cr{sub 2}N. The depth of the layer was 8.15 µm. The average hardness of the layer was 2160±15 HV{sub 0.025}. For uncoated and chromium nitride materials, wear rate increased with increasing load. The results of friction coefficient and wear rate of the tested materials showed that the CrN coating presents the lowest results.

Marine lowclouds have a large impact on the Earth’s energy and hydrologic cycle. They strongly reflect incoming solar radiation, with little compensating impact on outgoing longwave radiation resulting in a net cooling of the climate. The representation of marine lowclouds in climate models is one of the largest uncertainties in the estimation of climate sensitivity (e.g. Bony and Dufresne 2005), and marine lowclouds are critical mediators of global aerosol radiative forcing (Zelinka et al. 2014). Despite the importance of these cloud systems to the Earth’s climate, their parameterization continues to be challenging, due to an incomplete understanding of key processes that regulate them and insufficient resolution of these processes in models. To help define research pathways to address outstanding issues related to our understanding of marine lowclouds, a workshop was held January 27-29, 2016 at Brookhaven National Laboratory. The overarching goal was to identify current gaps in knowledge or simulation capabilities and promising strategies for addressing them, with a particular emphasis on improving the representation of marine lowclouds in climate models and contributions that could be made with U.S. Department of Energy Atmospheric System Research support using Atmospheric Radiation Measurement facility measurements.

We present a new overlay, called the Deterministic Decentralized tree (D2-tree). The D2-tree compares favorably to other overlays for the following reasons: (a) it provides matching and better complexities, which are deterministic for the supported operations; (b) the management of nodes (peers......-balancing scheme of elements into nodes is deterministic and general enough to be applied to other hierarchical tree-based overlays. This load-balancing mechanism is based on an innovative lazy weight-balancing mechanism, which is interesting in its own right....

Marine fog and lowclouds transfer water and nutrients to coastal ecosystems through advection from the ocean and reduce heat effects by reflecting incoming shortwave radiation. These effects are known to benefit many species, vegetation communities, and habitats such as coastal redwood trees and their understory, maritime chaparral, and coastal streams harboring endangered salmon species. The California floristic region is the highest ranked hotspot in the U.S. and ranked 7th of 35 biodiversity hotspots worldwide in terms of the percent of its plant species that are found nowhere else (endemic). Many environmental drivers have been identified as contributing to California's remarkably high endemism and biodiversity, however, coastal lowclouds have not typically been included. This could be due to the lack of data such as high resolution maps of coastal lowcloud occurrence or the lack of long term records. Using a recent analysis of hourly National Weather Service satellite data, a stability index (SI) for coastal fog and lowcloud cover was derived using two measures of variation and average summertime cloud cover to quantify long term spatial stability trends. Several discrete spatial clumps were identified that had both high temporal stability and high coastal lowcloud cover. These areas show a strong correlation with a specific topographic landscape configuration with respect to wind direction. Point occurrence distribution maps of endemic coastal species were overlain with the SI to explore spatial correlation. The federally endangered species that showed very high spatial correlation included Yadon's Rein-orchid (Piperia yadonii), Monterey Spineflower (Chorizanthe pungens var. pungens), and Seaside Bird's-beak (Cordylanthus rigidus ssp. littoralis). Current estimated range maps are not consistent with the SI results suggesting a need to update estimated ranges. Biodiversity measures are being investigated in these areas to explore the hypothesis that they

We have performed magnetic susceptibility, heat capacity, neutron powder diffraction, and muon spin relaxation experiments to investigate the magnetic ground states of the 5$d^2$ double perovskites Sr$_2$YReO$_6$ and Sr$_2$InReO$_6$. We find that Sr$_2$YReO$_6$ is a spin glass, while Sr$_2$InReO$_6$ hosts a non-magnetic singlet state. By making detailed comparisons with other 5$d^2$ double perovskites, we argue that a delicate interplay between spin-orbit coupling, non-cubic crystal fields, a...

A simple and computationally nonintensive technique based on principal component analysis of 3D fields to derive theoretical descriptors is presented. The descriptors are then applied to a quantitative structure-activity relationship study on some dopamine D2 antagonists of benzamide type.

A leading source of uncertainty in climate feedback arises from the representation of lowclouds, which are not resolved but depend on small-scale physical processes (e.g. entrainment, boundary layer turbulence) that are heavily parameterized. We show results from recent attempts to achieve an explicit representation of lowclouds by pushing the computational limits of cloud superparameterization to resolve boundary-layer eddy scales relevant to marine stratocumulus (250m horizontal and 20m vertical length scales). This extreme configuration is called "ultraparameterization". Effects of varying horizontal vs. vertical resolution are analyzed in the context of altered constraints on the turbulent kinetic energy statistics of the marine boundary layer. We show that 250m embedded horizontal resolution leads to a more realistic boundary layer vertical structure, but also to an unrealistic cloud pulsation that cannibalizes time mean LWP. We explore the hypothesis that feedbacks involving horizontal advection (not typically encountered in offline LES that neglect this degree of freedom) may conspire to produce such effects and present strategies to compensate. The results are relevant to understanding the emergent behavior of quasi-resolved lowcloud decks in a multi-scale modeling framework within a previously unencountered grey zone of better resolved boundary-layer turbulence.

Agaricus bisporus is a popular culinary-medicinal mushroom in Taiwan, and γ-irradiation could extend its shelf life. Our objective was to study the content of vitamin D2 and the taste components and antioxidant properties of ethanolic extracts from A. bisporus with various doses of γ-irradiation. After irradiation, the vitamin D2 content of 5-10 kGy irradiated mushrooms was in the range of 5.22-7.90 µg/g, higher than that of the unirradiated control (2.24 µg/g). For all treatments, the total content of soluble sugars and polyols ranged from 113 to 142 mg/g, and the monosodium glutamate-like components ranged from 6.57 to 13.50 mg/g, among which the 2.5 kGy irradiated sample has the highest content of flavor 5'-nucleotide. About antioxidant properties, 10 kGy irradiated samples exhibited lower EC50 values than did other samples. EC50 values were less than 5 mg/mL for ethanolic extracts. Total phenols were the major antioxidant components and the total content was 13.24-22.78 mg gallic acid equivalents/g. Based on the results obtained, γ-irradiation could be used to improve the vitamin D2 content and intensity of umami taste in fresh mushrooms. In addition, γ-irradiation not only maintained the antioxidant properties of mushrooms but also enhanced the antioxidant properties to some extent.

Full Text Available The subtropical lowcloud response to a climate with SST uniformly warmed by 2 K is analyzed in the SP- CAM superparameterized climate model, in which each grid column is replaced by a two-dimensional cloud-resolving model (CRM. Intriguingly, SP-CAM shows substantial lowcloud increases over the subtropical oceans in the warmer climate. The paper aims to understand the mechanism for these increases. The subtropical lowcloud increase is analyzed by sorting grid-column months of the climate model into composite cloud regimes using percentile ranges of lower tropospheric stability (LTS. LTS is observed to be well correlated to subtropical lowcloud amount and boundary layer vertical structure. The lowcloud increase in SP-CAM is attributed to boundary-layer destabilization due to increased clear-sky radiative cooling in the warmer climate. This drives more shallow cumulus convection and a moister boundary layer, inducing cloud increases and further increasing the radiative cooling. The boundary layer depth does not change substantially, due to compensation between increased radiative cooling (which promotes more turbulent mixing and boundary-layer deepening and slight strengthening of the boundary-layer top inversion (which inhibits turbulent entrainment and promotes a shallower boundary layer. The widespread changes in lowclouds do not appear to be driven by changes in mean subsidence.In a companion paper we use column-mode CRM simulations based on LTS-composite profiles to further study the lowcloud response mechanisms and to explore the sensitivity of lowcloud response to grid resolution in SP-CAM.

A three-dimensional potential energy surface for the ground electronic state of MgH2 has been constructed from 9030 symmetry-unique ab initio points calculated using the icMRCI+Q method with aug-cc-pVnZ basis sets for n=3, 4, and 5, with core-electron correlation calculated at the MR-ACPF level of theory using cc-pCVnZ basis sets, with both calculations being extrapolated to the complete basis set limit. Calculated spectroscopic constants of MgH2 and MgD2 are in excellent agreement with recent experimental results: for four bands of MgH2 and one band of MgD2 the root-mean-square (rms) band origin discrepancies were only 0.44 and 0.06 cm(-1), respectively, and the rms relative discrepancies in the inertial rotational constants (B[v]) were only 0.0196% and 0.0058%, respectively. Spectroscopic constants for MgHD were predicted using the same potential surface.

The influence of the deposition conditions on the surface morphology, crystal structure and deuterium retention of the tungsten layers formed by rf magnetron plasma sputtering in mixed atmosphere of D2, He and Ar, has been carried out. Helium containing deuterated tungsten layers (named He-WDx) on Cu/Si substrate demonstrate serious film damages with zones of cracks, fractures, flaking-off and large surface blisters. However, these kinds of damages do not happen on the He-WDx layers performed on mechanically polished polycrystalline Cu substrates because of larger surface roughness of the substrates. The crystal structure of the W layer greatly changes with the additional He in the layer, and large amounts of defects resulting in lattice expansion and X-diffraction peak broadening were produced in the W crystal. He in the W layer has direct impacts on D retention. Both D and He concentrations vary simultaneously with He fraction, attached negative bias and substrate temperature.

This work describes an investigation of the static (or quasistatic) nuclear magnetic resonance (NMR) response in a nematic liquid crystal confined between two planar conducting plates and subject to a magnetic field and an electric field produced by a difference of voltage applied on the plates. Deuterium NMR spectroscopy of 4-pentyl-d(2)-4'-cyanobiphenyl (5CB-d(2)) under these conditions has revealed a voltage dependent inhomogeneous director distribution for a particular narrow range of voltages and for a fixed magnetic field (that of the spectrometer). In the ideal setup the two plates are assumed to be rigorously parallel, so that a difference of voltage applied on the plates leads to a constant electric field normal to them. When the magnetic field is parallel to the plates (orthogonal geometry) there exists a threshold value of the electric field for which the effect of both fields exactly compensate; moreover, for stronger electric field the director aligns with the electric field while for weaker electric field the director aligns with the magnetic field. If there is a lack of parallelism between the two plates, the electric field becomes inhomogeneous so that it may be larger than the threshold value in some region of the sample and smaller in the remaining part of the sample. In that case the director will adopt essentially two orientations within the sample, namely, parallel or perpendicular to the magnetic field, and the position of the frontier between the two domains depends on the voltage. This feature is clearly shown by deuterium NMR spectra that exhibit a transfer of intensity between two quadrupolar doublets with increase in the applied voltage. The coexistence of two director populations occurs for a range of voltages that depends on the degree of nonparallelism; accordingly, an estimation of this range by NMR yields an experimental estimation of the lack of parallelism. A tiny tilt of the magnetic field (nonorthogonal geometry) entrains a

One of the biggest challenges facing Free-Space Optics deployment is proper understanding of optical signal propagation in different atmospheric conditions. In an earlier study by the author (30), attenuation by rain was analyzed and successfully modeled for infrared signal transmission. In this paper, we focus on attenuation due to scattering by haze, fog and lowclouds droplets using the original Mie Scattering theory. Relying on published experimental results on infrared propagation, electromagnetic waves scattering by spherical droplet, atmospheric physics and thermodynamics, UlmTech developed a computer-based platform, Simulight, which simulates infrared signal (750 nm-12 μm) propagation in haze, fog, lowclouds, rain and clear weather. Optical signals are scattered by fog droplets during transmission in the forward direction preventing the receiver from detecting the minimum required power. Weather databases describe foggy conditions by measuring the visibility parameter, which is, in general, defined as the maximum distance that the visible 550 nm signal can travel while distinguishing between the target object and its background at 2% contrast. Extrapolating optical signal attenuations beyond 550 nm using only visibility is not as straightforward as stated by the Kruse equation which is unfortunately widely used. We conclude that it is essential to understand atmospheric droplet sizes and their distributions based on measured attenuations to effectively estimate infrared attenuation. We focus on three types of popular fogs: Evolving, Stable and Selective.

Integrating nanomaterials with different dimensionalities and properties is a versatile approach toward realizing new functionalities in advanced devices. Here, a novel diode-type heterostructure is reported consisting of 1D semiconducting ZnO nanorods and 2D metallic LaAlO3-SrTiO3 interface. Tunable insulator-to-metal transitions, absent in the individual components, are observed as a result of the competing temperature-dependent conduction mechanisms. Detailed transport analysis reveals direct tunneling at low bias, Fowler-Nordheim tunneling at high forward bias, and Zener breakdown at high reverse bias. Our results highlight the rich electronic properties of such artificial diodes with hybrid dimensionalities, and the design principle may be generalized to other nanomaterials.

We examine the influence of southern African orography on the Namibian stratocumulus deck, the South Atlantic ocean-to-atmosphere energy transport, and the Intertropical Convergence Zone (ITCZ), using an atmosphere-only model and a coupled atmosphere-ocean model. For both models, a control simulation with realistic orography is compared to a simulation where the orography in southern Africa was removed. As in the previous studies, the removal of orography results in thinning of the Namibian stratocumulus deck. In the coupled model, the increased sea surface temperature in the southern Atlantic due to the reduction of lowclouds forces the Atlantic ITCZ to shift southward toward the warmer hemisphere. However, changes in the ocean circulation cool the South Atlantic atmosphere, lessening the ITCZ shift and changing the structure of precipitation. These results show the importance of orography on shaping Atlantic rainfall and highlight the role of dynamical ocean processes in atmospheric dynamics.

We extended the measurements of the rotational transitions of D2H+ up to 3 THz by using the JPL frequency multiplier chains and a TuFIR system at Toyama. D2H+ was generated in an extended negative glow discharge cell cooled to liquid nitrogen temperature. We observed five new THz lines. All the available rotational transition frequencies together with the combination differences derived from the three fundamental bands were subject to least square analysis to determine the molecular constants. New THz measurements are definitely useful for better characterization of spectroscopic properties. The improved molecular constants provide better predictions of other unobserved rotational transitions.

Arctic lowclouds strongly affect the Arctic surface energy budget. Through this impact Arctic lowclouds influence important aspects of the Arctic climate system, namely surface and atmospheric temperature, sea ice extent and thickness, and atmospheric circulation. Arctic clouds are in turn influenced by these elements of the Arctic climate system, and these interactions create the potential for Arctic cloud-climate feedbacks. To further our understanding of potential Arctic cloud-climate feedbacks, the goal of this paper is to quantify the influence of atmospheric state on the surface cloud radiative effect (CRE) and its covariation with sea ice concentration (SIC). We build on previous research using instantaneous, active remote sensing satellite footprint data from the NASA A-Train. First, the results indicate significant differences in the surface CRE when stratified by atmospheric state. Second, there is a weak covariation between CRE and SIC for most atmospheric conditions. Third, the results show statistically significant differences in the average surface CRE under different SIC values in fall indicating a 3-5 W m-2 larger LW CRE in 0% versus 100% SIC footprints. Because systematic changes on the order of 1 W m-2 are sufficient to explain the observed long-term reductions in sea ice extent, our results indicate a potentially significant amplifying sea ice-cloud feedback, under certain meteorological conditions, that could delay the fall freeze-up and influence the variability in sea ice extent and volume. Lastly, a small change in the frequency of occurrence of atmosphere states may yield a larger Arctic cloud feedback than any cloud response to sea ice.

Reactive mineral-water interfaces exert control on the bioavailability of contaminant arsenic species in natural aqueous systems. However, the ability to accurately predict As surface complexation is limited by the lack of molecular-level understanding of As-water-mineral interactions. In the present study, we report the structures and properties of the adsorption complexes of arsenous acid (As(OH)3) on hydrated mackinawite (FeS) surfaces, obtained from density functional theory (DFT) calculations. The fundamental aspects of the adsorption, including the registries of the adsorption complexes, adsorption energies, and structural parameters are presented. The FeS surfaces are shown to be stabilized by hydration, as is perhaps to be expected because the adsorbed water molecules stabilize the low-coordinated surface atoms. As(OH)3 adsorbs weakly at the water-FeS(001) interface through a network of hydrogen-bonded interactions with water molecules on the surface, with the lowest-energy structure calculated to be an As-up outer-sphere complex. Compared to the water-FeS(001) interface, stronger adsorption was calculated for As(OH)3 on the water-FeS(011) and water-FeS(111) interfaces, characterized by strong hybridization between the S-p and O-p states of As(OH)3 and the surface Fe-d states. The As(OH)3 molecule displayed a variety of chemisorption geometries on the water-FeS(011) and water-FeS(111) interfaces, where the most stable configuration at the water-FeS(011) interface is a bidentate Fe-AsO-Fe complex, but on the water-FeS(111) interface, a monodentate Fe-O-Fe complex was found. Detailed information regarding the adsorption mechanisms has been obtained via projected density of states (PDOS) and electron density difference iso-surface analyses and vibrational frequency assignments of the adsorbed As(OH)3 molecule.

Low ceiling and visibility is a weather hazard that nearly every forecaster, in nearly every National Weather Service (NWS) Weather Forecast Office (WFO), must regularly address. In addition, national forecast centers such as the Aviation Weather Center (AWC), Alaska Aviation Weather Unit (AAWU) and the Ocean Prediction Center (OPC) are responsible for issuing low ceiling and visibility related products. As such, reliable methods for detecting and characterizing hazardous lowclouds are needed. Traditionally, hazardous areas of Fog/Low Stratus (FLS) are identified using a simple stand-alone satellite product that is constructed by subtracting the 3.9 and 11 μm brightness temperatures. However, the 3.9-11 μm brightness temperature difference (BTD) has several major limitations. In an effort to address the limitations of the BTD product, the GOES-R Algorithm Working Group (AWG) developed an approach that fuses satellite, Numerical Weather Prediction (NWP) model, Sea Surface Temperature (SST) analyses, and other data sets (e.g. digital surface elevation maps, surface emissivity maps, and surface type maps) to determine the probability that hazardous lowclouds are present using a naïve Bayesian classifier. In addition, recent research has focused on blending geostationary (e.g. GOES-R) and low earth orbit (e.g. JPSS) satellite data to further improve the products. The FLS algorithm has adopted an enterprise approach in that it can utilize satellite data from a variety of current and future operational sensors and NWP data from a variety of models. The FLS products are available in AWIPS/N-AWIPS/AWIPS-II and have been evaluated within NWS operations over the last four years as part of the Satellite Proving Ground. Forecaster feedback has been predominantly positive and references to these products within Area Forecast Discussions (AFD's) indicate that the products are influencing operational forecasts. At the request of the NWS, the FLS products are currently being

Stratocumulus and shallow cumulus clouds in subtropical oceanic regions (e.g., Southeast Pacific) cover thousands of square kilometers and play a key role in regulating global climate (e.g., Klein and Hartmann, 1993). Numerical modeling is an essential tool to study these clouds in regional and global systems, but the current generation of climate and weather models has difficulties in representing them in a realistic way (e.g., Siebesma et al., 2004; Stevens et al., 2007; Teixeira et al., 2011). While numerical models resolve the large-scale flow, subgrid-scale parameterizations are needed to estimate small-scale properties (e.g. boundary layer turbulence and convection, clouds, radiation), which have significant influence on the resolved scale due to the complex nonlinear nature of the atmosphere. To represent the contribution of these fine-scale processes to the resolved scale, climate models use various parameterizations, which are the main pieces in the model that contribute to the lowclouds dynamics and therefore are the major sources of errors or approximations in their representation. In this project, we aim to 1) improve our understanding of the physical processes in thermal circulation and cloud formation, 2) examine the performance and sensitivity of various parameterizations in the regional weather model (Weather Research and Forecasting model; WRF), and 3) develop, implement, and evaluate the advanced boundary layer parameterization in the regional model to better represent stratocumulus, shallow cumulus, and their transition. Thus, this project includes three major corresponding studies. We find that the mean diurnal cycle is sensitive to model domain in ways that reveal the existence of different contributions originating from the Southeast Pacific land-masses. The experiments suggest that diurnal variations in circulations and thermal structures over this region are influenced by convection over the Peruvian sector of the Andes cordillera, while

, THOR produces results that are generally within the range of LES results, indicating that the single-column THOR is able to reproduce the gross characteristics of boundary layer clouds nearly as well as three-dimensional LES. Sensitivity to vertical grid spacing, diagnostic/prognostic third- order moments, choice of turbulence length scale entrainment process, and whether or not PDF sampling is used to drive the microphysics and radiation schemes is assessed for all test cases. Simulation of the cumulus regime was degraded when vertical grid spacing exceeded 200 m, when more third-order moments were predicted, when higher parcel entrainment rates were assumed, and when PDF sampling for the microphysics scheme was omitted. Simulation of stratocumulus was degraded with grid spacing larger than 100 m, when PDF sampling for microphysics was omitted, and when PDF sampling for radiation was included. Lastly, THOR is used to study lowcloud climate feedbacks in the northeastern Pacific Ocean in the context of the CGILS project. Initial conditions and forcings are supplied at 13 points along the GPCI cross-section that spans from the ITCZ northeast to the coast of California transecting regions of shallow cumuli and stratocumuli, for both the current climate and a climate with a +2K SST perturbation. A change in net cloud radiative forcing of 0-8 W/m-2 was simulated along the cross-section for the perturbed climate, representing neutral to weak positive feedback. The responsible mechanism appeared to be increased boundary layer entrainment and stratocumulus decoupling leading to reduced maximum cloud cover in the cumulus regime and reduced liquid water path in the stratocumulus regime.

Retreat of Arctic sea ice extent has led to more evaporation over open water in summer and subsequent cloud changes in autumn. Studying recent satellite cloud data over the Arctic Ocean, we find that low (0.5-2 km) cloud cover in October has been increasing significantly during 2000-2010 over the Beaufort and East Siberian Sea (BESS). This change is consistent with the expected boundary-layer cloud response to the increasing Arctic evaporation accumulated during summer. Because lowclouds have a net warming effect at the surface, October cloud increases may be responsible for the enhanced autumnal warming in surface air temperature, which effectively prolong the melt season and lead to a positive feedback to Arctic sea ice loss. Thus, the new satellite observations provide a critical support for the hypothesized positive feedback involving interactions between boundary-layer cloud, water vapor, temperature and sea ice in the Arctic Ocean.

PURPOSE: Nearly one billion people around the world are deficient in vitamin D and need to be supplemented. Vitamin D is available in medicines and fortified foods. It is available in two forms: vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). KEY POINTS: The pharmacopeiae consider these steroid hormones as equivalent and interchangeable. However, several studies have showed that serum level of 25(OH)D is increased more effectively with vitamin D3 than vitamin D2. Vitamin D2 has ...

The Nisku B and G pools are 2 W. Pembina D-2 pools with contrasting reservoir properties. Average porosity, permeability, and maximum thickness are 5%, 130 md, and 95 m; and 16.4%, 7100 md and 19 m, respectively. The results of the depletion model studies of waterflooding and miscible flooding and some of the problems that occurred during these studies are reviewed.

Hetero-oligomers of G-protein-coupled receptors have become the subject of intense investigation because their purported potential to manifest signaling and pharmacological properties that differ from the component receptors makes them highly attractive for the development of more selective pharmacological treatments. In particular, dopamine D1 and D2 receptors have been proposed to form hetero-oligomers that couple to Gαq proteins, and SKF83959 has been proposed to act as a biased agonist that selectively engages these receptor complexes to activate Gαq and thus phospholipase C. D1/D2 heteromers have been proposed as relevant to the pathophysiology and treatment of depression and schizophrenia. We used in vitro bioluminescence resonance energy transfer (BRET), ex vivo analyses of receptor localization and proximity in brain slices, and behavioral assays in mice to characterize signaling from these putative dimers/oligomers. We were unable to detect Gαq or Gα11 protein coupling to homomers or heteromers of D1 or D2 receptors using a variety of biosensors. SKF83959-induced locomotor and grooming behaviors were eliminated in D1 receptor knockout mice, verifying a key role for D1-like receptor activation. In contrast, SKF83959-induced motor responses were intact in D2 receptor and Gαq knockout mice, as well as in knock-in mice expressing a mutant Ala286-CaMKIIα, that cannot autophosphorylate to become active. Moreover, we found that in the shell of the nucleus accumbens, even in neurons in which D1 and D2 receptor promoters are both active, the receptor proteins are segregated and do not form complexes. These data are not compatible with SKF83959 signaling through Gαq or through a D1–D2 heteromer and challenge the existence of such a signaling complex in the adult animals that we used for our studies. PMID:25560761

Operations at Central-Spanish airports are often, especially in winter, affected by visibility reduction. The Instituto Nacional de Meteorología (INM), the Spanish Weather Service, has developed a single-column model (SCM) in order to improve short-term forecasts of fog, visibility and low-clouds. The SCM, called H1D, is a one-dimensional version of the HIRLAM limited-area model. It is operationally run for three airports in the region: Madrid-Barajas, Almagro and Albacete-Los Llanos. Since SCMs cannot deal with horizontal heterogeneity, the terms that depend on the horizontal structure of the atmosphere are estimated from the outputs of the three-dimensional (3-D) model and introduced into the SCM as external forcings. The systematic analysis of the meteorological situations has evidenced the existence of a close relationship between fog formation and the presence of drainage winds in the region. Since the 3-D model docs not have the necessary resolution to correctly simulate the main features of the drainage flow caused by the complex topography in the proximity of Madrid-Barajas, it cannot provide the SCM with the correct forcings. This problem has been partially overcome through the introduction of a module that, under certain conditions, substitutes the values computed from the 3-D model outputs by others that are based on a conceptual model of the phenomenon and have been empirically derived from climatological knowledge. This module improves the H1D verification scores for the basic meteorological variables—wind, temperature and humidity—and reduces the false alarm rate in fog forecast.

We performed molecular, enzyme, and metabolic studies in 50 patients with D-2-hydroxyglutaric aciduria (D-2-HGA) who accumulated D-2-hydroxyglutarate (D-2-HG) in physiological fluids. Presumed pathogenic mutations were detected in 24 of 50 patients in the D-2-hydroxyglutarate dehydrogenase (D2HGD...

Ergosterol (provitamin D(2)) is converted to vitamin D(2) in grass by exposure to UV light. Six varieties of perennial ryegrass (Lolium perenne L.) were harvested four times during the season, and the contents of vitamin D(2) and ergosterol were analyzed by a sensitive and selective liquid...... chromatography tandem mass spectrometry method. Weather factors were recorded, and a principal component analysis was performed to study which factors were important for the formation of vitamin D(2). The results suggest that a combination of weather factors is involved and that the contents of ergosterol...... and vitamin D(2) change more than a factor of 10 during the season. These results demonstrate that grass potentially can be a significant source of vitamin D for grazing animals and animals fed on silage and hay....

Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor) can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain. PMID:23637801

Full Text Available Under normal conditions the brain maintains a delicate balance between inputs of reward seeking controlled by neurons containing the D1-like family of dopamine receptors and inputs of aversion coming from neurons containing the D2-like family of dopamine receptors. Cocaine is able to subvert these balanced inputs by altering the cell signaling of these two pathways such that D1 reward seeking pathway dominates. Here, we provide an explanation at the cellular and biochemical level how cocaine may achieve this. Exploring the effect of cocaine on dopamine D2 receptors function, we present evidence of σ1 receptor molecular and functional interaction with dopamine D2 receptors. Using biophysical, biochemical, and cell biology approaches, we discovered that D2 receptors (the long isoform of the D2 receptor can complex with σ1 receptors, a result that is specific to D2 receptors, as D3 and D4 receptors did not form heteromers. We demonstrate that the σ1-D2 receptor heteromers consist of higher order oligomers, are found in mouse striatum and that cocaine, by binding to σ1 -D2 receptor heteromers, inhibits downstream signaling in both cultured cells and in mouse striatum. In contrast, in striatum from σ1 knockout animals these complexes are not found and this inhibition is not seen. Taken together, these data illuminate the mechanism by which the initial exposure to cocaine can inhibit signaling via D2 receptor containing neurons, destabilizing the delicate signaling balance influencing drug seeking that emanates from the D1 and D2 receptor containing neurons in the brain.

Full Text Available Abstract Introduction: oil in water emulsions has attracted considerable food industry due to their physical characteristics. But there is a considerable amount of cholesterol in some of them, such as cream and it was a risk factor for cardiovascular disease and are created compounds in the effect of cholesterol oxidation during processing or food storage compounds that are known as carcinogenic agents, cytotoxic, mutagenic and atherogenic. The purpose of this study is the production of cream mixed with cholesterol and lower prices and greater nutritional value than dairy cream. Methods: Three different formulations of the mixture cream (A, B, C, soy milk, cow's milk, water soluble emulsifier, xanthan, calcium chloride, light cream milk, sunflower oil and emulsifier Sytrum was taken in proportions appropriate. The Pearson correlation was used to assess the relationship between amounts of fat, protein with water. Sensory evaluation of the cream mixture samples was conducted by using a 9-point Hedonic scale. They were used rank Kruskal-Wallis test Due to the response variables. They were used the specific test of multiple comparisons DAN for compare the two groups. They were also used descriptive statistics as mean and standard deviation and were performed data analysis by using R 2.3 software. Results: the Pearson correlation coefficient between fat and.16 volume (increase volume is equal to 45% and p-value B (p <0.05. Conclusion: The results of this study showed that the use of soy milk made ​​from soy flour, although somewhat affecting flavor and creamy mixed water but while increasing the nutritional properties can be formulated with other ingredients to create the perfect texture.

Silylenes (silanediyls) have made an important impact on organosilicon chemistry even if it is of more recent foundation than carbenes in organic chemistry and much less complete. These species are highly reactive intermediates. They play a central role in the chemical vapour deposition (CVD) of various silicon-containing thin films which have a technological importance in microelectronics as well as in the dry etching processes of silicon wafers. Spectroscopic methods have been developed to observe these species, a necessary pre-requisite to their direct monitoring. In this work, deuterated phenylsilane precursor, PhSiD3 was chosen for SiD2 because its analogue phenylsilane, PhSiH3 proved to be a good precursor for SiH2 and the high quality decay signals observed revealed that SiD2 be readily detected from PhSiD3 and that if other decomposition pathways (e.g. PhSiD + D2) are occurring, they do not effect measurements of the rate constants for SiD2. The absorption spectrum of SiD2 formed from the flash photolysis of a mixture of PhSiD3 and SF6 at 193nm were found in the region 17384-17391 cm-1 with strong band at 17387.07 cm-1. This single rotational line of pQ1 was chosen to monitor SiD2 removal. Time-resolved studies of SiD2 have been carried out to obtain rate constants for its bimolecular reactions with D2. The reactions were studied over the pressure range 5-100 Torr (in SF6 bath gas) at four temperatures in the range 298-498K. Single decay from 10 photolysis laser shots were averaged and found to give reasonable first-order kinetics fits. Second order kinetics were obtained by pressure dependence of the pseudo first order decay constants and substance D2 pressures within experimental error. The reaction was found to be weakly pressure dependent at all temperatures, consistent with a third-body mediated association process. In addition, SiH2+ H2 reaction is approximately ca. 60% faster than SiD2+D2 reaction. Theoretical extrapolations (using Lindemann

Full Text Available Silylenes (silanediyls have made an important impact on organosilicon chemistry even if it is of more recent foundation than carbenes in organic chemistry and much less complete. These species are highly reactive intermediates. They play a central role in the chemical vapour deposition (CVD of various silicon-containing thin films which have a technological importance in microelectronics as well as in the dry etching processes of silicon wafers. Spectroscopic methods have been developed to observe these species, a necessary pre-requisite to their direct monitoring. In this work, deuterated phenylsilane precursor, PhSiD3 was chosen for SiD2 because its analogue phenylsilane, PhSiH3 proved to be a good precursor for SiH2 and the high quality decay signals observed revealed that SiD2 be readily detected from PhSiD3 and that if other decomposition pathways (e.g. PhSiD + D2 are occurring, they do not effect measurements of the rate constants for SiD2. The absorption spectrum of SiD2 formed from the flash photolysis of a mixture of PhSiD3 and SF6 at 193nm were found in the region 17384-17391 cm-1 with strong band at 17387.07 cm-1. This single rotational line of pQ1 was chosen to monitor SiD2 removal. Time-resolved studies of SiD2 have been carried out to obtain rate constants for its bimolecular reactions with D2. The reactions were studied over the pressure range 5-100 Torr (in SF6 bath gas at four temperatures in the range 298-498K. Single decay from 10 photolysis laser shots were averaged and found to give reasonable first-order kinetics fits. Second order kinetics were obtained by pressure dependence of the pseudo first order decay constants and substance D2 pressures within experimental error. The reaction was found to be weakly pressure dependent at all temperatures, consistent with a third-body mediated association process. In addition, SiH2+ H2 reaction is approximately ca. 60% faster than SiD2+D2 reaction. Theoretical extrapolations (using

The structure of some glucosamine Schiff bases has been studied by means of ab initio RHF and DFT calculation and CP/MAS 13C and 15N NMR measurements. The anomeric and tautomeric equilibria in a DMSO solution have been studied by 1H, 13C and 15N NMR spectroscopy. The anomeric composition of D-2-glucosamine Schiff bases in the solid state and in DMSO solution has been shown to depends on the tautomeric form of Schiff bases and electronic properties of substituents on the aromatic ring.

Gastric cancer is one of the most common causes of cancer death worldwide. Surgery is the most widely utilized treatment for resectable gastric cancer. Evidence indicates that lymph node involvement and depth of invasion of the primary tumor are the most important prognostic factors for gastric cancer patients. Therefore, lymph node clearance is deemed a key procedure in gastric cancer surgery for the prognostic value to patients. Although the appropriate lymphadenectomy during gastrectomy for cancer still remains controversial, extended lymph node dissection (D2 lymphadenectomy) should be recommended in high volume hospitals.

We show how one can systematically construct vacuum solutions to Einstein field equations with $D-2$ commuting Killing vectors in $D>4$ dimensions. The construction uses Einstein-scalar field seed solutions in 4 dimensions and is performed both for the case when all the Killing directions are spacelike, as well as when one of the Killing vectors is timelike. The later case corresponds to generalizations of stationary axially symmetric solutions to higher dimensions. Some examples representing generalizations of known higher dimensional stationary solutions are discussed in terms of their rod structure and horizon locations and deformations.

Full Text Available Abstract Background The assembly of neural circuits requires the concerted action of both genetically determined and activity-dependent mechanisms. Calcium-regulated transcription may link these processes, but the influence of specific transcription factors on the differentiation of synapse-specific properties is poorly understood. Here we characterize the influence of NeuroD2, a calcium-dependent transcription factor, in regulating the structural and functional maturation of the hippocampal mossy fiber (MF synapse. Results Using NeuroD2 null mice and in vivo lentivirus-mediated gene knockdown, we demonstrate a critical role for NeuroD2 in the formation of CA3 dendritic spines receiving MF inputs. We also use electrophysiological recordings from CA3 neurons while stimulating MF axons to show that NeuroD2 regulates the differentiation of functional properties at the MF synapse. Finally, we find that NeuroD2 regulates PSD95 expression in hippocampal neurons and that PSD95 loss of function in vivo reproduces CA3 neuron spine defects observed in NeuroD2 null mice. Conclusion These experiments identify NeuroD2 as a key transcription factor that regulates the structural and functional differentiation of MF synapses in vivo.

Several error structures for weighted regression equations used for predicting volume were examined for 2 large data sets of felled and standing loblolly pine trees (Pinus taeda L.). The generally accepted model with variance of error proportional to the value of the covariate squared ( D2H = diameter squared times height or D...

An important property of the reproducing kernel of D2(Ω, ρ) is obtained and the reproducing kernels for D2(Ω, ρ) are calculated when Ω = Bn × Bn and ρ are some special functions. A reproducing kernel is used to construct a semi-positive definite matrix and a distance function defined on Ω×Ω. An inequality is obtained about the distance function and the pseudodistance induced by the matrix.

A surrogate climate change is designed to investigate lowcloud feedbacks in the northeastern Pacific by using Single Column Models (SCMs), Cloud Resolving Models (CRMs), and Large Eddy Simulation models (LES), as part of the CGILS study (CFMIP-GASS Intercomparison of LES and SCM models). The constructed large-scale forcing fields, including subsidence and advective tendencies, and their perturbations in the warmer climate are shown to compare well with conditions in General Circulation Models (GCMs), but they are free from the impact of any GCM parameterizations. The forcing fields in the control climate are also shown to resemble the mean conditions in the ECMWF-Interim Reanalysis. Applications of the forcing fields in SCMs are presented. It is shown that the idealized design can offer considerable insight into the mechanisms of cloud feedbacks in the models. Caveats and advantages of the design are also discussed.

An exact fully-localized extremal supergravity solution for N_2 D2 branes and N_6 D6 branes, which is dual to 3-dimensional supersymmetric SU(N_2) gauge theory with N_6 fundamentals, was found by Cherkis and Hashimoto. In order to consider the thermal properties of the gauge theory we present the non-extremal extension of this solution to first order in an expansion near the core of the D6 branes. We compute the Hawking temperature and the black brane horizon area/entropy. The leading order entropy, which is proportional to N_2^{3/2} N_6^{1/2} T_H^2, is not corrected to first order in the expansion. This result is consistent with the analogous weak-coupling result at the correspondence point N_2 ~ N_6.

Laxemar candidate area is located in the province of Smaaland, some 320 km south of Stockholm. The area is located close to the shoreline of the Baltic Sea and is within the municipality of Oskarshamn, and immediately west of the Oskarshamn nuclear power plant and the Central interim storage facility for spent fuel (Clab). The easternmost part (Simpevarp subarea) includes the Simpevarp peninsula, which hosts the power plants and the Clab facility. The island of Aespoe, containing the Aespoe Hard Rock Laboratory is located some three kilometres northeast of the central parts of Laxemar. The Laxemar subarea covers some 12.5 km2, compared with the Simepvarp subarea, which is approximately 6.6 km2. The Laxemar candidate area has been investigated in stages, referred to as the initial site investigations (ISI) and the complete site investigations (CSI). These investigations commenced in 2002 and were completed in 2008. During the site investigations, several studies and design steps (D0, D1 and D2) were carried out to ensure that sufficient space was available for the 6,000-canister layout within the target volume at a depth of approximately 500 m. The findings from design Step D2 for the underground facilities including the access ramp, shafts, rock caverns in a Central Area, transport tunnels, and deposition tunnels and deposition holes are contained in this report. The layout for these underground excavations at the deposition horizon requires an area of 5.7 km2, and the total rock volume to be excavated is 3,008 x 103 m3 using a total tunnel length of approximately 115 km. The behaviour of the underground openings associated with this layout is expected to be similar to the behaviour of other underground openings in the Scandinavian shield at similar depths. The dominant mode of instability is expected to be structurally controlled wedge failure. Stability of the openings will be achieved with traditional underground rock support and by orienting the openings

Quantum molecular sieving separability of D(2) from an H(2)-D(2) mixture was measured at 77 K for activated carbon fiber, carbon molecular sieve, zeolite and single wall carbon nanotube using a flow method. The amount of adsorbed D(2) was evidently larger than H(2) for all samples. The maximum adsorption ratio difference between D(2) and H(2) was 40% for zeolite (MS13X), yielding a selectivity for D(2) with respect to H(2) of 3.05.

We discuss the symmetry properties and the macroscopic behavior of a nematic liquid crystal phase with D2d symmetry. Such a phase is a prime candidate for nematic phases made from banana-shaped molecules where the usual quadrupolar order coexists with octupolar (tetrahedratic) order. The resulting nematic phase is non-polar. While this phase could resemble the classic D∞h nematic in the polarizing microscope, it has many static as well as reversible and irreversible properties unknown to non-polar nematics without octupolar order. In particular, there is a linear gradient term in the free energy that selects parity leading to ambidextrously helical ground states when the molecules are achiral. In addition, there are static and irreversible coupling terms of a type only met otherwise in macroscopically chiral liquid crystals, e.g. the ambidextrous analogues of Lehmann-type effects known from cholesteric liquid crystals. Finally, we discuss certain nonlinear aspects of the dynamics related to the non-commutativity of three-dimensional finite rotations as well as other structural nonlinear hydrodynamic effects.

Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [(35)S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction.

Dopamine D2 autoreceptors located on the midbrain dopaminergic neurons modulate dopamine (DA) neuron firing, DA release, and DA synthesis through a negative-feedback mechanism. Dysfunctional D2 autoreceptors following repeated drug exposure could lead to aberrant DA activity in the ventral tegmental area (VTA) and projection areas such as nucleus accumbens (NAcc), promoting drug-seeking and -taking behavior. Therefore, it is important to understand molecular mechanisms underlying drug-induced changes in D2 autoreceptors. Here, we reported that 5 days of amphetamine (AMPH) self-administration reduced the ability of D2 autoreceptors to inhibit DA release in the NAcc as determined by voltammetry. Using the antibody-capture [35S]GTPγS scintillation proximity assay, we demonstrated for the first time that midbrain D2/D3 receptors were preferentially coupled to Gαi2, whereas striatal D2/D3 receptors were coupled equally to Gαi2 and Gαo for signaling. Importantly, AMPH abolished the interaction between Gαi2 and D2/D3 receptors in the midbrain while leaving striatal D2/D3 receptors unchanged. The disruption of the coupling between D2/D3 receptors and Gαi2 by AMPH is at least partially explained by the enhanced RGS2 (regulator of G-protein signaling 2) activity resulting from an increased RGS2 trafficking to the membrane. AMPH had no effects on the midbrain expression and trafficking of other RGS proteins such as RGS4 and RGS8. Our data suggest that midbrain D2/D3 receptors are more susceptible to AMPH-induced alterations. Reduced D2 autoreceptor function could lead to enhanced DA signaling and ultimately addiction-related behavior. RGS2 may be a potential non-dopaminergic target for pharmacological intervention of dysfunctional DA transmission and drug addiction. PMID:24513972

It is known that dopamine (DA) D2 receptor availability in basal ganglia decreases with age. This study was done to assess the effects of age on extrastriatal DA D2 receptors. DA D2 receptor availability was evaluated in 42 healthy male subjects (age mean 41 {plus_minus} 16, range 21 -86 year old) using positron emission tomography (PET) and [C-11]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen, thalamus, frontal, occipital cortices, temporal insula, cingulate and orbitofrontal gyri) to that in the cerebellum which is a function of B{sub max.}/K{sub d}. Pearson product-moment correlation was used to evaluate the correlation between age and D2 receptor availability. DA D2 receptor availability in putamen (r {le} 0.0001), caudate (r {le} 0.0002), thalamus (r {le} 0.03), and temporal insula (r {le} 0.01) were significantly correlated with age. The decrements in D2 receptors with age were lower in extrastriatal than in striatal regions and corresponded to a decrease of 4.7% per decade in caudate, 6.2% in putamen, 2.1% in thalamus and 2.5% in temporal insula. This study documents age related decrement of DA D2 receptor availability in striatal and extrastriatal regions.

The Device-to-Device (D2D) communication system is an important part of heterogeneous networks. It has great potential to improve spectrum efficiency, throughput and energy efficiency cooperation of multiple D2D users with the advantage of direct communication. When cooperating, D2D users expend extraordinary energy to relay data to other D2D users. Hence, the remaining energy of D2D users determines the life of the system. This paper proposes a cooperation scheme for multiple D2D users who reuse the orthogonal spectrum and are interested in the same data by aiming to solve the energy problem of D2D users. Considering both energy availability and the Signal to Noise Ratio (SNR) of each D2D user, the Kuhn-Munkres algorithm is introduced in the cooperation scheme to solve relay selection problems. Thus, the cooperation issue is transformed into a maximum weighted matching (MWM) problem. In order to enhance energy efficiency without the deterioration of Quality of Service (QoS), the link outage probability is derived according to the Shannon Equation by considering the data rate and delay. The simulation studies the relationships among the number of cooperative users, the length of shared data, the number of data packets and energy efficiency.

An exact fully-localized extremal supergravity solution for N{sub 2} D2-branes and N{sub 6} D6-branes, which is dual to 3-dimensional supersymmetric SU(N{sub 2}) gauge theory with N{sub 6} fundamentals, was found by Cherkis and Hashimoto. In order to consider the thermal properties of the gauge theory we present the non-extremal extension of this solution to first order in an expansion near the core of the D6-branes. We compute the Hawking temperature and the black-brane horizon area/entropy. The leading-order entropy, which is proportional to N{sub 2}{sup 3/2}N{sub 6}{sup 1/2}T{sub H}{sup 2}, is not corrected to first order in the expansion. This result is consistent with the analogous weak-coupling result at the correspondence point N{sub 2} similar to N{sub 6}.

We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS{sub 3} x S{sup 3} x S{sup 3} warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS{sub 3} x S{sup 3} x S{sup 3} x R {sup 2}, modulo discrete identifications of the flat R {sup 2}, and (ii) that solutions with γ < 0 cannot have more than one asymptotic higher-dimensional AdS region. We classify the allowed singularities of h and G near the boundary of Σ, and identify four local solutions: asymptotic AdS{sub 4}/Z{sub 2} or AdS{sub 7}' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ <0, and the Janus solution for γ > 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS{sub 4}/Z{sub 2} for γ < 0, and conjecture that they are a different superconformal limit of the self-dual string. Finally, we construct exactly γ > 0 solutions with highly curved M5

Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.

Stimulated by the recent observation of the $D_2^\\ast(3000)$, we study the decay behaviors of the $3P$ and $2F$ charmed mesons in the present work. By comparing the masses and decay properties of the $3^3P_2$ and $2^3F_2$ charmed mesons with the observation of the $D_2^\\ast(3000)$, we conclude that the most possible assignment of the $D_2^\\ast(3000)$ is the $3^3P_2$ charmed meson, while the assignment of the $2^3F_2$ charmed meson could not be fully exclude. The results of the unobserved $3P$ and $2F$ charmed mesons in this work could provide some fundamental information of searching for these charmed mesons in the further experiments by LHCb and forthcoming Belle II.

The topic of this doctoral dissertation is registration of 3D medical images to corresponding projective 2D images, referred to as 3D/2D registration. There are numerous possible applications of 3D/2D registration in image-aided diagnosis and treatment. In most of the applications, 3D/2D registration provides the location and orientation of the structures in a preoperative 3D CT or MR image with respect to intraoperative 2D X-ray images. The proposed doctoral dissertation tries to find origin...

Following our previous work on fractional spin symmetries (FSS) \\cite{2, 4}, we build here a superspace representation of the heterotic $D=2(1/3,0)$ superalgebra and derive a field theoretical model invariant under this symmetry.

Full Text Available AbstractPatients with malignant gliomas have a poor prognosis with average survival of less than one year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG, a metabolite, which was discovered first in this tumor entity. D2HG is generated in large amounts due to various gain-of–function mutations in the isocitrate dehydrogenases IDH-1 and IDH-2. Meanwhile, D2HG has been detected in several other tumor entities including intrahepatic bile-duct cancer, chondrosarcoma, acute myeloid leukemia, and angioimmunoblastic T-cell lymphoma. D2HG is barely detectable in healthy tissue (< 0.1 mM, but its concentration increases up to 35 mM in malignant tumor tissues. Consequently, the oncometabolite D2HG has gained increasing interest in the field of tumor metabolism. To facilitate its quantitative measurement without loss of spatial resolution at a microscopical level, we have developed a novel bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography / mass spectrometry (LC/MS. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0 – 10 µmol/g tissue (wet weight. In combination with the already established bioluminescence imaging techniques for ATP, glucose, pyruvate, and lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual tumors in a further dimension.

Molecular dynamics calculations have been performed to study the ultraviolet photodissociation of D2O in an amorphous D2O ice surface at 10-90 K, in order to investigate the influence of isotope effects on the photodesorption processes. As for H2O, the main processes after UV photodissociation are trapping and desorption. There are three desorption processes: D atom, OD radical, and D2O molecule photodesorption. D2O desorption takes places either by direct desorption of a recombined D2O molecule, or when an energetic D atom produced by photodissociation kicks a surrounding D2O molecule out of the surface by transferring part of its momentum. Desorption probabilities are compared quantitatively with those for H2O obtained from previous MD simulations of UV photodissociation of amorphous water ice. The main conclusions are the same, but the average D atom photodesorption probability is smaller than that of the H atom (by about a factor of 0.9) because D has lower kinetic energy than H, whereas the average OD ra...

Elucidating the neurobiological mechanisms underlying individual differences in the extent to which reward cues acquire the ability to act as incentive stimuli may contribute to the development of successful treatments for addiction and related disorders. We used the sign-tracker/goal-tracker animal model to examine the role of dopamine D2 and D3 receptors in the propensity to attribute incentive salience to reward cues. Following Pavlovian training, wherein a discrete lever-cue was paired with food reward, rats were classified as sign- or goal-trackers based on the resultant conditioned response. We examined the effects of D2/D3 agonists, 7-OH-DPAT (0.01–0.32 mg/kg) or pramipexole (0.032–0.32 mg/kg), the D2/D3 antagonist raclopride (0.1 mg/kg), and the selective D3 antagonist, SB-277011A (6 or 24 mg/kg), on the expression of sign- and goal-tracking conditioned responses. The lever-cue acquired predictive value and elicited a conditioned response for sign- and goal-trackers, but only for sign-trackers did it also acquire incentive value. Following administration of either 7-OH-DPAT, pramipexole, or raclopride, the performance of the previously acquired conditioned response was attenuated for both sign- and goal-trackers. For sign-trackers, the D2/D3 agonist, 7-OH-DPAT, also attenuated the conditioned reinforcing properties of the lever-cue. The selective D3 antagonist did not affect either conditioned response. Alterations in D2/D3 receptor signaling, but not D3 signaling alone, transiently attenuate a previously acquired Pavlovian conditioned response, regardless of whether the response is a result of incentive motivational processes. These findings suggest activity at the dopamine D2 receptor is critical for a reward cue to maintain either its incentive or predictive qualities. PMID:26909847

An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string the...... theory. This leads to a new construction of vector valued modular forms which exhibits some of the features of a generalized Hecke transform.......An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string...

An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string theory. This leads to a new construction of vector valued modular forms which exhibit some of the features of a generalized Hecke transform.

An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string theory. This leads to a new construction of vector valued modular forms which exhibits some of the features of a generalized Hecke transform.

An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string...... theory. This leads to a new construction of vector valued modular forms which exhibits some of the features of a generalized Hecke transform....

The direct photodissociation of D2 at excitation energies above 14.76 eV occurs via two channels, D (2 s )+D (1 s ) and D (2 p )+D (1 s ) . The branching ratios between the two have been measured from the dissociation threshold to 3200 cm-1 above it, and it is found that they show cosine oscillations as a function of the fragment wave vector magnitudes. The oscillation is due to an interference effect and can be simulated using the phase difference between the wave functions of the two channels, analogous to Young's double-slit experiment. By fitting the measured branching ratios, we have determined the depths and widths of the effective spherical potential wells related to the two channels, which are in agreement with the effective depths and widths of the ab initio interaction potentials. The results of this Letter illustrate the importance of the relative phase between the fragments in controlling the branching ratios of the photodissociation channels.

Full Text Available Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and ropinirole. Our results show that acetaldehyde was able to induce and maintain a drug-taking behaviour, displaying an escalation during training, and a reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant drinking behaviour involved D2-receptor signalling: in particular, quinpirole administration at 0.03 mg/kg, induced a significant decrease in the number of lever presses both in extinction and in relapse. Ropinirole, administered at 0.03 mg/kg during extinction, did not produce any modification but, when administered during abstinence, induced a strong decrease in acetaldehyde intake in the following relapse session. Taken together, our data suggest that acetaldehyde exerts its own motivational properties, involving the dopaminergic transmission: indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction and relapse, negatively affects operant behaviour for acetaldehyde, likely decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic D2-receptors by ropinirole, during abstinence, decreases the motivation to the consecutive reinstatement of acetaldehyde drinking behaviour, likely counteracting the reduction in the dopaminergic tone typical of withdrawal. These data further

Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and ropinirole. Our results show that acetaldehyde was able to induce and maintain a drug-taking behaviour, displaying an escalation during training, and a reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant drinking behaviour involved D2-receptor signalling: in particular, quinpirole administration at 0.03 mg/kg, induced a significant decrease in the number of lever presses both in extinction and in relapse. Ropinirole, administered at 0.03 mg/kg during extinction, did not produce any modification but, when administered during abstinence, induced a strong decrease in acetaldehyde intake in the following relapse session. Taken together, our data suggest that acetaldehyde exerts its own motivational properties, involving the dopaminergic transmission: indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction and relapse, negatively affects operant behaviour for acetaldehyde, likely decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic D2-receptors by ropinirole, during abstinence, decreases the motivation to the consecutive reinstatement of acetaldehyde drinking behaviour, likely counteracting the reduction in the dopaminergic tone typical of withdrawal. These data further strengthen the evidence

Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC) and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC. PMID:25814948

Full Text Available The dopaminergic system has been shown to control the amount of noise in the prefrontal cortex (PFC and likely plays an important role in working memory and the pathophysiology of schizophrenia. We developed a model that takes into account the known receptor distributions of D1 and D2 receptors, the changes these receptors have on neuron response properties, as well as identified circuitry involved in working memory. Our model suggests that D1 receptor under-stimulation in supragranular layers gates internal noise into the PFC leading to cognitive symptoms as has been proposed in attention disorders, while D2 over-stimulation gates noise into the PFC by over-activation of cortico-striatal projecting neurons in infragranular layers. We apply this model in the context of a memory-guided saccade paradigm and show deficits similar to those observed in schizophrenic patients. We also show set-shifting impairments similar to those observed in rodents with D1 and D2 receptor manipulations. We discuss how the introduction of noise through changes in D1 and D2 receptor activation may account for many of the symptoms of schizophrenia depending on where this dysfunction occurs in the PFC.

We present results of MD calculations performed to study the photodissociation of D2O in an amorphous ice at different ice temperatures in order to investigate isotope effects on the photodesorption processes. In dense interstellar clouds, small dust particles of micrometer silicates are covered by ice mantles, mainly consisting of H2O and also of CO, CO2. Previous MD calculations of H2O ice at Tice=10-90 K show that the photodesorption of H while OH remains trapped is the main outcome in the first three monolayers (MLs). On the other hand, the H and OH photofragments released recombine or are trapped at separate positions in the deeper MLs and can react with other species in the ice. Desorption and trapping probabilities have been calculated following photoexcitation of D2O amorphous ice at 10, 20, 60 and 90 K, and the main conclusions agree with previous calculations of H2O ice. But, the average D photodesorption probability is smaller than that of the H atom, whereas the average OD radical photodesorption probability is larger than that of OH, and the average D2O photodesorption probability is larger than that for H2O due to the D2O kick-out mechanism. The total (OD + D2O) yield has been compared with experiments and the total (OH + H2O) yield from previous simulations. We find better agreement when we compare experimental yields with calculated yields for D2O ice than when we compare with calculated yields for H2O ice.

Distribution in Multiple Musical Gestures (D2MMG) uses a robust interface for detecting simple drawing gestures. The gestures affect low- and high-level aspects of sound and music through inherent modes organized as primary and secondary gestures. This enables expressive live performance...... and improvisation with sequence creation where musical elements such as tonality, chromaticity, rhythm patterns, and melodical sequences can be affected in real-time. We introduce a utility for procedurally controlling note density and chordal alignment. Future papers will focus on D2MMG’s progressive learning...

Distribution in Multiple Musical Gestures (D2MMG) uses a robust interface for detecting simple drawing gestures. The gestures affect low- and high-level aspects of sound and music through inherent modes organized as primary and secondary gestures. This enables expressive live performance...... and improvisation with sequence creation where musical elements such as tonality, chromaticity, rhythm patterns, and melodical sequences can be affected in real-time. We introduce a utility for procedurally controlling note density and chordal alignment. Future papers will focus on D2MMG’s progressive learning...

RATIONALE: Accumulating evidence indicates that the cognitive effects of dopamine depend on the subtype of dopamine receptor that is activated. In particular, recent work with animals as well as current theorizing has suggested that cognitive flexibility depends on dopamine D2 receptor signaling.

Although several studies suggest that dopamine D2 receptor (DRD2) gene may contribute to creativity, the relationship between DRD2 and creativity still needs to be further validated. To further test the relevance of DRD2 and creativity, this study explored the association between DRD2 and creative ideation in 483 unrelated healthy Chinese…

We suggest a method of bosonizing any D=2 theory. We demonstrate how it works with the examples of the Thirring and the Schwinger models, known results are reproduced. This method, being applied to the Gross-Neveu model, yields nonlinear boson WZW-type theory with additional constraint in the field space. Relation to the nonlinear sigma - model is also discussed.

Dispersion interactions play a crucial role in noncovalently bound molecular systems, and recent studies have shown that dispersion effects are also critical for accurately describing covalently bound solids. While most studies on bulk solids have solely focused on equilibrium properties (lattice constants, bulk moduli, and cohesive energies), there has been little work on assessing the importance of dispersion effects for solid-state properties far from equilibrium. In this work, we present a detailed analysis of both equilibrium and highly nonequilibrium properties (tensile strengths leading to fracture) of various palladium-hydride systems using representative DFT methods within the LDA, GGA, DFT-D2, DFT-D3, and nonlocal vdw-DFT families. Among the various DFT methods, we surprisingly find that the empirically constructed DFT-D2 functional gives extremely anomalous and qualitatively incorrect results for tensile strengths in palladium-hydride bulk solids. We present a detailed analysis of these effects and discuss the ramifications of using these methods for predicting solid-state properties far from equilibrium. Most importantly, we suggest caution in using DFT-D2 (or other coarse-grained parametrizations obtained from DFT-D2) for computing material properties under large stress/strain loads or for evaluating solid-state properties under extreme structural conditions.

G d2S n2O7 and G d2T i2O7 have been regarded as good experimental realizations of the classical Heisenberg pyrochlore antiferromagnet with dipolar interaction. The former was found to adopt the Palmer-Chalker state via a single, first-order transition at TN≈1 K , while the latter enters a distinct, partially ordered state through two successive transitions at TN 1≈1 K and TN 2= 0.75 K . To shed more light on their distinct magnetic ground states, we have synthesized two more gadolinium-based pyrochlore oxides, G d2G e2O7 and G d2P t2O7 , under high-pressure conditions and performed detailed characterizations via x-ray powder diffraction, dc and ac magnetic susceptibility, and specific heat measurements down to 100 mK. We found that both compounds enter a long-range antiferromagnetically ordered state through a single, first-order transition at TN= 1.4 K for G d2G e2O7 and TN= 1.56 K for G d2P t2O7 , with the specific heat anomaly similar to that of G d2S n2O7 rather than G d2T i2O7 . Interestingly, the low-temperature magnetic specific heat values of both G d2G e2O7 and G d2P t2O7 were found to follow nicely the T3 dependence as expected for a three-dimensional antiferromagnet with gapless spin-wave excitations. We have rationalized the enhancement of TN in terms of the reduced Gd-Gd distances for the chemically pressurized G d2G e2O7 and the addition of extra superexchange pathways through the empty Pt -eg orbitals for G d2P t2O7 . Our current study has expanded the family of gadolinium-based pyrochlores and permits us to achieve a better understanding of their distinct magnetic properties in a more comprehensive perspective.

Applications of 3-D2-e systems have proliferated very fast due to technological advancements in wide range of phenomena from atomic landscape to mesoscopic scale. The unusual properties of atomic/mesoscopic systems are the results of interplaying charge interactions among different bound states. The non-trivial e-e correlations in electrically and/or magnetically confined systems improvise wealth of intriguing challenges at fundamental level due to lack of exact solution of Schrödinger equations. For the first time, a novel methodology of exactly finite summed coulomb correlations invented by us is so handy that even usual programmable calculator can be used to examine the electronic structures of 3-D2-e harmonic dots in perpendicular magnetic field (symmetric gauge). Statistics of electronic levels, heat capacity measurements and magnetization (T∼1 K) are also investigated in brief to probe the degree of disorderedness.

The addition of supersymmetric Chern-Simons terms to ${\\cal N}=8$ super-Yang-Mills theory in three-dimensions is expected to make the latter flow into infrared superconformal phases. We address this problem holographically by studying the effect of the Romans mass on the D2-brane near-horizon geometry. Working in a consistent, effective four-dimensional setting provided by $D=4$ ${\\cal N}=8$ supergravity with a dyonic $\\textrm{ISO(7)}$ gauging, we verify the existence of a rich web of supersymmetric domain walls triggered by the Romans mass that interpolate between the (four-dimensional description of the) D2-brane and various superconformal phases. We also construct domain walls for which both endpoints are superconformal. While most of our results are numerical, we provide analytic results for the $\\textrm{SU}(3)\\times \\textrm{U}(1)$-invariant flow into an ${\\cal N}=2$ conformal phase recently discovered.

The addition of supersymmetric Chern-Simons terms to N=8 super-Yang-Mills theory in three-dimensions is expected to make the latter flow into infrared superconformal phases. We address this problem holographically by studying the effect of the Romans mass on the D2-brane near-horizon geometry. Working in a consistent, effective four-dimensional setting provided by D=4N=8 supergravity with a dyonic ISO(7) gauging, we verify the existence of a rich web of supersymmetric domain walls triggered by the Romans mass that interpolate between the (four-dimensional description of the) D2-brane and various superconformal phases. We also construct domain walls for which both endpoints are superconformal. While most of our results are numerical, we provide analytic results for the SU(3)×U(1)-invariant flow into an N=2 conformal phase recently discovered.

The perchlorate ion (ClO4-) has garnered particular interest in recent years following the discovery of perchlorate salts in the Martian regolith at levels of 0.4-0.6 wt% by the Phoenix lander in 2006 and Mars Science Laboratory's Curiosity rover in 2013. Due to their oxidizing properties, perchlorates are suspected to play a contributing role to the surprising lack of organics on the Martian surface. In this study, magnesium perchlorate hexahydrate (Mg(ClO4)2●6H2O) samples were irradiated with monoenergetic beams of 5 keV electrons and D2+ ions separately, sequentially, and simultaneously to simulate the effects of galactic cosmic ray exposure of perchlorates. The irradiation experiments were carried out under ultra-high vacuum conditions at 50 K, after which the samples were slowly heated to 300 K (0.5 K min-1) while desorbing products were monitored by quadrupole mass spectrometry. In all cases, molecular oxygen (O2) was detected upon the onset of irradiation and again during the warmup phase. In the case of simultaneous irradiation, deuterated water (D2O) and deuterium peroxide (D2O2) were also detected as the sample was heated whereas in the D2+ experiment small amounts of D2O2 was found exclusively. When samples were irradiated sequentially, the production of D2O2 was dependent upon the sample being irradiated with D2+ ions prior to electrons. These experiments show that perchlorates are capable of producing multiple oxidizing agents (O2, D2O2) which may also account for the lack of organics on the Martian surface.

The D2 vibrons have been studied by high-resolution Raman scattering in mixed crystals of (p-D2)x(o-D2)1-x. The o-D2 and p-D2 vibrational transitions are found to overlap. Line shapes calculated by the coherent potential approximation are in good qualitative agreement with the experimental data. The linewidth of the o-D2 transition is much larger than the linewidth of the p-H2 transition in (o-H2)x(p-H2)1-x mixed crystals with comparable J=1 concentrations. Possible explanations for this difference are discussed.

The recombinant human prostaglandin D2 (PGD2) receptor, hCRTH2, has been expressed in HEK293(EBNA) and characterized with respect to radioligand binding and signal transduction properties. High and low affinity binding sites for PGD2 were identified in the CRTH2 receptor population by saturation analysis with respective equilibrium dissociation constants (KD) of 2.5 and 109 nM. This revealed that the affinity of PGD2 for CRTH2 is eight times less than its affinity for the DP receptor.Equilibr...

Using the crossed-beam machine EVA measurements have been conducted of the product angular and energy distributions of the reaction O(-) + D2 yields OD(-) + D in the relative energy range of 1.2-4.7 eV (5.7-23.1 eV LAB). Below 2.5 eV the product distribution is centered about the center of mass, indicating a long-lived complex. Above 2.5 eV the distribution slowly moves forward. Most of the available energy goes into internal energy of the products.

Huntington's disease, an inherited neurodegenerative disorder, results from abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted in synergy with expanded huntingtin to increase aggregates formation and striatal death through activation of the Rho/ROCK signaling pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin expression in the rat striatum, we found that the D2 antagonist haloperidol protects striatal neurons against expanded huntingtin-mediated toxicity. Two variant transcripts are generated by alternative splicing of the of D2 receptor gene, the D2R-Long and the D2R-Short, which are thought to play different functional roles. We show herein that overexpression of D2R-Short, but not D2R-Long in cell lines is associated with activation of the RhoA/ROCK signaling pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole triggers phosphorylation of cofilin, a downstream effector of ROCK, which is abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs targeting D2R-Long alone. Aggregate formation and neuronal death induced by expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R-Short but not D2R-Long alone. Our data provide evidence for a specific coupling of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK signaling in Huntington's disease is unraveled with our findings.

The short and long isoforms of the dopamine D2 receptor (D2S and D2L respectively) are highly expressed in the striatum. Functional D2 receptors activate an intracellular signalling pathway that includes a cAMP-independent route involving Akt/GSK3 (glycogen synthase kinase 3). To investigate the Akt/GSK3 response to the seldom-studied D2S receptor, we established a rat D2S receptor-expressing cell line [HEK (human embryonic kidney)-293/rD2S]. We found that in HEK-293/rD2S cells, the D2/D3 agonists bromocriptine and quinpirole significantly induced Akt and GSK3 phosphorylation, as well as ERK1/2 (extracellular-signal-regulated kinase 1/2) activation. The D2S receptor-induced Akt signals were profoundly inhibited by the internalization blockers monodansyl cadaverine and concanavalin A. Activation of the D2S receptor in HEK-293/rD2S cells appeared to trigger Akt/phospho-Akt translocation to the cell membrane. In addition to our cell culture experiments, we studied D2 receptor-dependent Akt in vivo by systemic administration of the D2/D3 agonist quinpirole. The results show that quinpirole evoked Akt-Ser473 phosphorylation in the ventral striatum. Furthermore, intra-accumbens administration of wortmannin, a PI3K (phosphoinositide 3-kinase) inhibitor, significantly suppressed the quinpirole-evoked behavioural activation. Overall, we demonstrate that activation of the dopamine D2S receptor stimulates Akt/GSK3 signalling. In addition, in vivo Akt activity in the ventral striatum appears to play an important role in systemic D2/D3 agonist-induced behavioural activation.

Full Text Available The short and long isoforms of the dopamine D2 receptor (D2S and D2L respectively are highly expressed in the striatum. Functional D2 receptors activate an intracellular signalling pathway that includes a cAMP-independent route involving Akt/GSK3 (glycogen synthase kinase 3. To investigate the Akt/GSK3 response to the seldom-studied D2S receptor, we established a rat D2S receptor-expressing cell line [HEK (human embryonic kidney-293/rD2S]. We found that in HEK-293/rD2S cells, the D2/D3 agonists bromocriptine and quinpirole significantly induced Akt and GSK3 phosphorylation, as well as ERK1/2 (extracellular-signal-regulated kinase 1/2 activation. The D2S receptor-induced Akt signals were profoundly inhibited by the internalization blockers monodansyl cadaverine and concanavalin A. Activation of the D2S receptor in HEK-293/rD2S cells appeared to trigger Akt/phospho-Akt translocation to the cell membrane. In addition to our cell culture experiments, we studied D2 receptor-dependent Akt in vivo by systemic administration of the D2/D3 agonist quinpirole. The results show that quinpirole evoked Akt-Ser473 phosphorylation in the ventral striatum. Furthermore, intra-accumbens administration of wortmannin, a PI3K (phosphoinositide 3-kinase inhibitor, significantly suppressed the quinpirole-evoked behavioural activation. Overall, we demonstrate that activation of the dopamine D2S receptor stimulates Akt/GSK3 signalling. In addition, in vivo Akt activity in the ventral striatum appears to play an important role in systemic D2/D3 agonist-induced behavioural activation.

We report the first interstellar detection of c-C3D2. The doubly deuterated cyclopropenylidene, a carbene, has been detected toward the starless cores TMC- 1C and L1544 using the IRAM 30m telescope. The J(Ka,Kc) = 3(0,3)-2(1,2), 3(1,3)-2(0,2), and 2(2,1)-1(1,0) transitions of this species have been observed at 3 mm in both sources. The expected 1:2 intensity ratio has been found in the 3(0,3)-2(1,2) and 3(1,3)-2(0,2) lines, belonging to the para and ortho species respectively. We also observed lines of the main species, c-C3H2, the singly deuterated c-C3HD, and the species with one 13C off of the principal axis of the molecule, c-H13CC2H. The lines of c-C3D2 have been observed with high signal to noise ratio, better than 7.5 sigma in TMC-1C and 9 sigma in L1544. The abundance of doubly deuterated cyclopropenylidene with respect to the normal species is found to be (0.4 - 0.8)% in TMC-1C and (1.2 - 2.1)% in L1544. The deuteration of this small hydrocarbon ring is analysed with a comprehensive gas-grain model, ...

Drugs that induce psychosis, such as -amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd 2 −/−), we first investigated whether D2 is required for AMP disruption ...

We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;\\gamma) \\oplus D(2,1;\\gamma). Their space-time has the form AdS_3 x S^3 x S^3 warped over a Riemann surface \\Sigma. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (\\gamma, h, G), where \\gamma is the real parameter of the isometry superalgebra, and h and G are functions on \\Sigma whose differential equations and regularity conditions depend only on the sign of \\gamma. The magnitude of \\gamma enters only through the map of h, G onto the supergravity fields, thereby promoting all solutions into families parametrized by |\\gamma|. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS_3 x S^3 x S^3 x R^2, modulo discrete identifications ...

We present a generalization of the standard Inoenue-Wigner contraction by rescaling not only the generators of a Lie superalgebra but also the arbitrary constants appearing in the components of the invariant tensor. The procedure presented here allows one to obtain explicitly the Chern-Simons supergravity action of a contracted superalgebra. In particular we show that the Poincare limit can be performed to a D = 2 + 1 (p,q) AdS Chern-Simons supergravity in presence of the exotic form. We also construct a new three-dimensional (2,0) Maxwell Chern-Simons supergravity theory as a particular limit of (2,0) AdS-Lorentz supergravity theory. The generalization for N = p + q gravitinos is also considered. (orig.)

The infrared spectrum of ν2 of D2S was recorded from 740 to 1100 cm -1 on the University of Denver 50-cm FTIR spectrometer system. We have assigned 655 transitions from D 232S and 129 from D 234S, and have analyzed them using Watson's A-reduced Hamiltonian evaluated in the I r representation. We used the recently published D 232S and D 234S ground state Hamiltonian constants [C. Camy-Peyret, J. M. Flaud, L. Lechuga-Fossat and J. W. C. Johns, J. Mol. Spectrosc.109, 300-333 (1985)]. Upper state Hamiltonian constants were obtained from a fit of the ν2 transitions, keeping the ground state constants fixed while varying the upper state constants. The standard deviation of the D 232S ν2 fit is 0.0025 cm -1. The standard deviation of the D 234S ν2 fit is 0.0041 cm -1.

The Stark effect of the sodium D2 line was investigated by use of high-resolution laser-atomic-beam spectroscopy. The shift and splitting of the hyperfine components of the line could be obtained and compared with theoretical calculations. This allows the determination of the scalar and tensor polarizabilities with high accuracy to be 49.28(15) and -21.97(10) kHz/(kV/cm)2, respectively. These values are compared with semiempirical calculated polarizabilities. Additionally, the behavior of the relative intensity of the components could be studied. In fields greater than 100 kV/cm, the two groups of components with MJ=(1/2 and (3/2 are widely separated and the pattern of each group is independent from the field strength, showing an ``electrical'' Paschen-Back effect. The relative intensities agree satisfactorily with the computations.

Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards.

Research in non-human primates has implicated striatal dopamine (D2) receptor function in the expression of social dominance--a fundamental component of social extraversion. We predicted that trait extraversion - indexed by the revised Eysenck Personality Questionnaire (EPQ-R) - would correlate with striatal DA (D2) receptor measures - indexed by [(11)C]-Raclopride binding potential (BP) - in 28 healthy post-menopausal females (mean age=75 years; range=58-91 years). Region of interest (ROI) and voxel-based statistical parametric mapping (SPM) analyses were performed, using a reference tissue model for [(11)C]-Raclopride. ROI analysis showed moderately significant negative correlations between extraversion and BP measures in the left caudate and between psychoticism scores and BP in the right putamen. Unexpectedly, scores on the Lie scale, a measure of socially desirable responding, were significantly and negatively correlated with BP measures in the putamen and survived Bonferroni correction on the right side. After controlling for the potential confounding of self-report bias in high Lie scorers, only the correlation between Lie scores and BP measures in the right putamen remained significant. Voxel-based analysis showed only Lie scores to be significantly and negatively correlated with BP measures in the right putamen. We explored this association further by applying an ROI-based approach to data on a previously scanned sample of young adults (n=13) and found a similar pattern of association, which achieved trend level significance in the right putamen. Although unanticipated, the relationship observed between BP measures in the right putamen and Lie scores is consistent with dopaminergic involvement in socially rewarding behaviour. How this relates to dopaminergic tone will need to be further explored.

We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over AdS{sub 4} x M{sup 7} {sup vertical} {sup stroke} {sup 6} spaces, where we use S{sup 7}/Z{sub k} and CP{sup 3} for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis- Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of SO(8) and SU(4) x U(1), and it agrees with a marginal boundary operator of the conformal dimension of Δ{sub +} = 3. However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized AdS{sub 4} space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all N = 8, 6 supersymmetries to N = 0, while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations 8s and 8v for the supercharges and scalars, respectively, while the fermions remain fixed in 8c of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full U(N){sub k} x U(N){sub -k} gauge group along the same lines with a similar situation to the one faced in the AdS{sub 5}/CFT{sub 4} correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for k = 1, 2 as well. (orig.)

Dopamine D2 and D3 autoreceptors are located on presynaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the rewarding properties of drugs of abuse. Using background subtracted fast scan cyclic voltammetry, we investigated the effects of dopamine D2 and D3 agonists on electrically stimulated dopamine release and uptake rates in the mouse caudate putamen and nucleus accumbens core and shell. The dopamine D2 agonists (−)-quinpirole hydrochloride and 5,6,7,8-tetrahydro-6-(2-propen-1-yl)-4H-thiazolo[4,5-d]azepin-2-amine dihydrochloride (B-HT 920) had the same dopamine release inhibition effects on caudate putamen and nucleus accumbens (core and shell) on the basis of their EC50 values and efficacies. This suggests that the dopamine D2 autoreceptor functionality is comparable in all three striatal regions investigated. The dopamine D3 agonists (4aR,10bR)-3,4a,4,10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol hydrochloride ((+)-PD 128907) and (±)-7-Hydroxy-2-dipropylaminotetralin hydrobromide (7-OH-DPAT) had a significantly greater effect on dopamine release inhibition in the nucleus accumbens shell than in the caudate putamen. This study confirms that, the dopamine D3 autoreceptor functionality is greater in the nucleus accumbens shell followed by the nucleus accumbens core, with the caudate putamen having the least. Neither dopamine D2 nor D3 agonists affected the uptake rates in nucleus accumbens but concentrations greater than 0.1 μM lowered the uptake rate in caudate putamen. To validate our method of evaluating dopamine D2 and D3 autoreceptors, sulpiride (D2 antagonist) and nafadotride (D3 antagonist) were used to reverse the effects of the dopamine agonists to approximately 100% of the preagonist

以核亲本品种鉴26和耐盐品种科遗26为对照,设计3种NaCl浓度(85.56 mmol/L, 171.04 mmol/L, 256.67 mmol/L)处理及无盐对照,研究了异源细胞质小麦D2-鉴26苗期的生长发育和生理生化特征.结果表明,D2型细胞质对核基因型鉴26存在明显的耐盐性遗传效应,效应值的大小因性状而异,核基因型鉴26与科遗26之间也存在差异;盐胁迫下,D2型细胞质能有效降低核基因型鉴26的生长受抑程度,提高其叶片相对含水量RWC,减轻其细胞质膜损伤度和增强对K+的选择性吸收能力,改变叶片功能蛋白的表达.这些研究结果表明,D2型细胞质是小麦耐盐育种的有用资源;异质系D2-鉴26是一个新的耐盐种质材料,其生长发育和渗透调节等相关耐盐特征可以作为D2型细胞质小麦遗传育种耐盐选择的有用指标;D2型细胞质小麦耐盐相关机制的阐明与利用也必将丰富小麦耐盐育种途径.%Alloplasmic wheat D2-'Jian 26', euplasmic wheat'Jian 26' and salt-tolerant control cultivar `Keyi 26' were evaluated in developmental and physiological traits at seedling stage under four levels of NaCl (0 mmol/L, 85.56 mmol/L, 171.04 mmol/L, 256.67 mmol/L). Significant genetic effects of D2-type cytoplasm on salt tolerance and genotypic differences in salt tolerance were observed. A clear improvement in terms of the developmental and physiological behaviours of D2-'Jian 26' and 'Jian 26' was demonstrated for alloplasmic line D2-'Jian 26'. In view of its better salt-tolerance compared with 'Keyi 26' and 'Jian 26', D2-'Jian 26' could be used as a new salt-tolerant germplasm. Under the low or medium salt-concentration, more root branching, large SK, Na(uptake) and SK, Na(transport), and good properties of leaf (relatively higher RWC and relatively lower cell-membrane damage and relatively higher chlorophyll content) were the potential usefulness as a salinity stress avoidance mechanism, suggesting that these parameters in stress

Ice-rock mixtures are found in a range of natural terrestrial and planetary environments. To understand how flow processes occur in these environments, laboratory-derived properties can be extrapolated to natural conditions through flow laws. Here, deformation experiments have been carried out on polycrystalline samples of pure ice, ice-rock and D2O-ice-rock mixtures at temperatures of 263, 253 and 233 K, confining pressure of 0 and 48 MPa, rock fraction of 0-50 vol.% and strain-rates of 5 × 10(-7) to 5 × 10(-5) s(-1) Both the presence of rock particles and replacement of H2O by D2O increase bulk strength. Calculated flow law parameters for ice and H2O-ice-rock are similar to literature values at equivalent conditions, except for the value of the rock fraction exponent, here found to be 1. D2O samples are 1.8 times stronger than H2O samples, probably due to the higher mass of deuterons when compared with protons. A gradual transition between dislocation creep and grain-size-sensitive deformation at the lowest strain-rates in ice and ice-rock samples is suggested. These results demonstrate that flow laws can be found to describe ice-rock behaviour, and should be used in modelling of natural processes, but that further work is required to constrain parameters and mechanisms for the observed strength enhancement.This article is part of the themed issue 'Microdynamics of ice'.

A review of the history of antipsychotics reveals that while the therapeutic effects of chlorpromazine and reserpine were discovered and actively researched almost concurrently, subsequent drug development has been restricted to drugs acting on postsynaptic receptors rather than modulation of dopamine release. The fundamental property of atypical antipsychotics is their ability to produce an antipsychotic effect in the absence of extrapyramidal side effects (EPS) or prolactin elevation. Modulation of the dopamine D2 receptor remains both necessary and sufficient for antipsychotic drug action, with affinity to the D2-receptor being the single most important discriminator between a typical and atypical drug profile. Most antipsychotics, including atypical antipsychotics, show a dose-dependent threshold of D2 receptor occupancy for their therapeutic effects, although the precise threshold is different for different drugs. Some atypical antipsychotics do not appear to reach the threshold for EPS and prolactin elevation, possibly accounting for their atypical nature. To link the biological theories of antipsychotics to their psychological effects, a hypothesis is proposed wherein psychosis is a state of aberrant salience of stimuli and ideas, and antipsychotics, via modulation of the mesolimbic dopamine system, dampen the salience of these symptoms. Thus, antipsychotics do not excise psychosis: they provide the neurochemical platform for the resolution of symptoms. Future generations of antipsychotics may need to move away from a "one-size-fits-all polypharmacy-in-a-pill" approach to treat all the different aspects of schizophrenia. At least in theory a preferred approach would be the development of specific treatments for the different dimensions of schizophrenia (e.g., positive, negative, cognitive, and affective) that can be flexibly used and titrated in the service of patients' presenting psychopathology.

Ice-rock mixtures are found in a range of natural terrestrial and planetary environments. To understand how flow processes occur in these environments, laboratory-derived properties can be extrapolated to natural conditions through flow laws. Here, deformation experiments have been carried out on polycrystalline samples of pure ice, ice-rock and D2O-ice-rock mixtures at temperatures of 263, 253 and 233 K, confining pressure of 0 and 48 MPa, rock fraction of 0-50 vol.% and strain-rates of 5 × 10-7 to 5 × 10-5 s-1. Both the presence of rock particles and replacement of H2O by D2O increase bulk strength. Calculated flow law parameters for ice and H2O-ice-rock are similar to literature values at equivalent conditions, except for the value of the rock fraction exponent, here found to be 1. D2O samples are 1.8 times stronger than H2O samples, probably due to the higher mass of deuterons when compared with protons. A gradual transition between dislocation creep and grain-size-sensitive deformation at the lowest strain-rates in ice and ice-rock samples is suggested. These results demonstrate that flow laws can be found to describe ice-rock behaviour, and should be used in modelling of natural processes, but that further work is required to constrain parameters and mechanisms for the observed strength enhancement. This article is part of the themed issue 'Microdynamics of ice'.

The phenomenon of RNA interference (RNAi) has been found in various organisms. However, the proteins implicated in RNAi pathway in different species show distinct roles. Knowledge on the underlying mechanism of lepidopteron RNAi is quite lacking such as the roles of Loquacious (Loqs) and R2D2, the dsRNA-binding proteins in silkworm RNAi pathway. Here, we report that Loqs and R2D2 protein depletion affected efficiency of dsRNA-mediated RNAi pathway. Besides, Loqs was found to co-localize with Dicer2 to some specific cytoplasmic foci, which were looked like D2-bodies marked by R2D2 and Dicer2 in Fly cells, thereby calling the foci as D2 body-like granules. Using RNAi methods, Loqs was found to be the key protein in these granules, although R2D2 determined the localization of Loqs in D2 body-like granules. Interestingly, in the R2D2-depeted silkworm cells, the formation of processing bodies, another cytoplasmic foci, was affected. These data indicated R2D2 regulated these two kinds of cytoplasmic foci. Domain deletion analysis demonstrated that dsRBD 1 and 2 were required for Loqs in D2 body-like granules and dsRBD 2 and 3 were required for Loqs to interact with R2D2 and Ago1, respectively. Altogether, our observations provide important information for further study on D2 body-like granules, the newly found cytoplasmic foci in silkworm cells.

A pulsed Nd:YAG laser at 355nm is used to pump Raman cell filled with D2,D2/Ar and D2/He.With adequately adjusted parameters,the maximum photon conversion efficiency of the first-order Stokes light(S1,396.796nm)reaches 33.33％ in D2/Ar and the stability of S1 in pure D2 is fairly high,the energy drift being less than 10％ when the pump energy drifts in the range of 5％.The conversion efficiency and stability,which are functions of the composition and pressure of the Raman medium and the energy of pump laser,are investigated.The result has been used to optimize the laser transmitter system for a differential absorption lidar system to measure NO2 concentration profiles.

Full Text Available The evaporation rate of D2O has been determined by Raman thermometry of a droplet train (12–15 μm diameter injected into vacuum (~10-5 torr. The cooling rate measured as a function of time in vacuum was fit to a model that accounts for temperature gradients between the surface and the core of the droplets, yielding an evaporation coefficient (γe of 0.57±0.06. This is nearly identical to that found for H2O (0.62±0.09 using the same experimental method and model, and indicates the existence of a kinetic barrier to evaporation. The application of a recently developed transition-state theory (TST model suggests that the kinetic barrier is due to librational and hindered translational motions at the liquid surface, and that the lack of an isotope effect is due to competing energetic and entropic factors. The implications of these results for cloud and aerosol particles in the atmosphere are discussed.

We find new higher derivative models describing a parity doublet of massive spin-3 modes in D =2 +1 dimensions. One of them is of fourth order in derivatives while the other one is of sixth order. They are complete, in the sense that they contain the auxiliary scalar field required to remove spurious degrees of freedom. Both of them are obtained through the master action technique starting with the usual (second-order) spin-3 Singh-Hagen model, which guarantees that they are ghost free. The fourth- and sixth-order terms are both invariant under (transverse) Weyl transformations, quite similarly to the fourth-order K -term of the "new massive gravity." The sixth-order term slightly differs from the product of the Schouten by the Einstein tensor, both of third order in derivatives. It is also possible to write down the fourth-order term as a product of a Schouten-like by an Einstein-like tensor (both of second order in derivatives) in close analogy with the K -term.

In rats, the discriminative stimulus effects of direct- and indirect-acting dopamine receptor agonists are mediated by multiple dopamine receptor subtypes and the relative contribution of dopamine D2 and D3 receptors to these effects varies as a function of feeding condition. In these studies, free-fed and food-restricted mice were trained to discriminate 10.0mg/kg cocaine using a two-lever discrimination procedure in which responding was maintained by food. Both groups of mice acquired the discrimination; however, free-fed mice responded at lower rates than food-restricted mice. Dopamine D3 receptor agonists, pramipexole and quinpirole, increased cocaine-appropriate responding (>85%) in food-restricted, but not in free-fed mice. The dopamine D2 receptor agonist, sumanirole, and the nonselective dopamine receptor agonist, apomorphine, failed to increase cocaine-appropriate responding in either group. Free-fed mice were more sensitive than food-restricted mice to the rate-decreasing effects of dopamine receptor agonists and these effects could not be overcome by increasing the magnitude of reinforcement. Because feeding condition did not alter quinpirole-induced hypothermia, it is unlikely that differences in the discriminative stimulus or rate-decreasing effects of dopamine D2-like receptor agonists were due to differences in the pharmacokinetic properties of the drugs. Although these results suggest that the discriminative stimulus effects of cocaine are mediated by both dopamine D2 and D3 receptors in food-restricted mice, the increased sensitivity of free-fed mice to the rate-decreasing effects of dopamine D2-like receptor agonists limited conclusions about the impact of feeding conditions on the relative contribution of dopamine D2 and D3 receptors to the discriminative stimulus effects of cocaine.

(S)-N-((1-Ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-3-iodo-6- methoxybenzamide (({sup 123}I)IBZM) is a central nervous system (CNS) D-2 dopamine receptor imaging agent. In order to investigate the versatility of this parent structure in specific dopamine receptor localization and the potential for developing new dopamine receptor imaging agents, a series of new iodinated benzamides with fused ring systems, naphthalene (INAP) and benzofuran (IBF), was synthesized and radiolabeled, and the in vivo and in vitro biological properties were characterized. The best analogue of IBZM is IBF (21). The specific binding of ({sup 125}I)IBF (21) with rat striatal tissue preparation was found to be saturable and displayed a Kd of 0.106 {plus minus} 0.015 nM. Competition data of various receptor ligands for ({sup 125}I)IBF (21) binding show the following rank order of potency: spiperone greater than IBF (21) greater than IBZM greater than (+)-butaclamol greater than ({plus minus})-ADTN,6,7 greater than ketanserin greater than SCH-23390 much greater than propranolol. The in vivo biodistribution results confirm that ({sup 125}I)IBF (21) concentrated in the striatal area after iv injection into rats. The study demonstrates that ({sup 123}I)IBF (21) is a potential agent for imaging CNS D-2 dopamine receptors.

We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH) screen, we identified the palmitoyl acyltransferase (PAT) zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R.

Full Text Available We have used bioorthogonal click chemistry (BCC, a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R, a G protein-coupled receptor (GPCR crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443 of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH screen, we identified the palmitoyl acyltransferase (PAT zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R.

Rapid solidification of D2 tool steel is investigated experimentally using electromagnetic levitation (EML) under terrestrial and reduced gravity conditions and impulse atomization (IA), a drop tube type of apparatus. IA produces powders 300 to 1400 μm in size. This allows the investigation of a large range of cooling rates ( 100 to 10,000 K/s) with a single experiment. On the other hand, EML allows direct measurements of the thermal history, including primary and eutectic nucleation undercoolings, for samples 6 to 7 mm in diameter. The final microstructures at room temperature consist of retained supersaturated austenite surrounded by eutectic of austenite and M7C3 carbides. Rapid solidification effectively suppresses the formation of ferrite in IA, while a small amount of ferrite is detected in EML samples. High primary phase undercoolings and high cooling rates tend to refine the microstructure, which results in a better dispersion of the eutectic carbides. Evaluation of the cell spacing in EML and IA samples shows that the scale of the final microstructure is mainly governed by coarsening. Electron backscattered diffraction (EBSD) analysis of IA samples reveals that IA powders are polycrystalline, regardless of the solidification conditions. EBSD on EML samples reveals strong differences between the microstructure of droplets solidified on the ground and in microgravity conditions. While the former ones are polycrystalline with many different grains, the EML sample solidified in microgravity shows a strong texture with few much larger grains having twinning relationships. This indicates that fluid flow has a strong influence on grain refinement in this system.

Full Text Available In this paper, we recall the linear version of the lattice Boltzmann schemes in the framework proposed by d’Humières. According to the equivalent equations we introduce a definition for a scheme to be isotropic at some order. This definition is chosen such that the equivalent equations are preserved by orthogonal transformations of the frame. The property of isotropy can be read through a group operation and then implies a sequence of relations on relaxation times and equilibrium states that characterizes a lattice Boltzmann scheme. We propose a method to select the parameters of the scheme according to the desired order of isotropy. Applying it to the D2Q9 scheme yields the classical constraints for the first and second orders and some non classical for the third and fourth orders.

The multidimensional string objects are introduced as a new alternative for an application of string models for time series forecasting in trading on financial markets. The objects are represented by open string with 2-endpoints and D2-brane, which are continuous enhancement of 1-endpoint open string model. We show how new object properties can change the statistics of the predictors, which makes them the candidates for modeling a wide range of time series systems. String angular momentum is proposed as another tool to analyze the stability of currency rates except the historical volatility. To show the reliability of our approach with application of string models for time series forecasting we present the results of real demo simulations for four currency exchange pairs.

Though D2 lymphadenectomy has been increasingly regarded as standard surgical procedure for advanced gastric cancer (GC), the modified D2 (D1 + 7, 8a and 9) lymphadenectomy may be more suitable than D2 dissection for T2 stage GC. The purpose of this study is to elucidate whether the surgical outcome of modified D2 lymphadenectomy was comparable to that of standard D2 dissection in T2 stage GC patients. A retrospective cohort study with 77 cases and 77 controls matched for baseline characteristics was conducted. Patients were categorized into two groups according to the extent of lymphadenectomy: the modified D2 group (mD2) and the standard D2 group (D2). Surgical outcome and recurrence date were compared between the two groups. The 5-year overall survival (OS) rate was 71.4% for patients accepted mD2 lymphadenectomy and 70.1% for those accepted standard D2, respectively, and the difference was not statistically significant. Multivariate survival analysis revealed that curability, tumor size, TNM stage and postoperative complications were independently prognostic factors for T2 stage GC patients. Patients in the mD2 group tended to have less intraoperative blood loss (P=0.001) and shorter operation time (PD2 group. While there were no significant differences in recurrence rate and types, especially lymph node recurrence, between the two groups. The surgical outcome of mD2 lymphadenectomy was equal to that of standard D2, and the use of mD2 instead of standard D2 can be a better option for T2 stage GC.

Carbon dioxide (CO2) ices were irradiated with energetic D+ ions to simulate the exposure of oxygen-bearing solar system ices to energetic protons from the solar wind and magnetospheric sources. The formation of species was observed online and in situ by exploiting FTIR spectroscopy. Molecular products include ozone (O3), carbon oxides (CO3(C 2v , D 3h ), CO4, CO5, CO6), D2-water (D2O), and D2-carbonic acid (D2CO3). Species released into the gas phase were sampled via a quadrupole mass spectrometer, and possible minor contributions from D2-formaldehyde (D2CO), D4-methanol (CD3OD), and D2-formic acid (DCOOD) were additionally identified. The feasibility of several reaction networks was investigated by determining their ability to fit the observed temporal column densities of 10 key species that were quantified during the irradiation period. Directly relevant to the CO2-bearing ices of comets, icy satellites in the outer solar system, and the ice caps on Mars, this work illustrates for the first time that D2-water is formed as a product of the exposure of CO2 ices to D+ ions. These findings provide strong support for water formation from oxygen-bearing materials via non-thermal hydrogen atoms, and predict reaction pathways that are likely to be unfolding on the surfaces of asteroids and the Moon.

Agrobacterium tumefaciens is a pathogenic bacterium, which can genetically transform plants and other organisms. It does so by translocating a part of its DNA, the T-strand, in complex with the relaxase protein VirD2. We have shown that VirD2 is the determinant of translocation of the VirD2-T-strand

Dysfunction of D2-like receptors has been reported in essential hypertension. Disruption of D2R in mice (D2-/-) results in high blood pressure, and several D2R polymorphisms are associated with decreased D2R expression. Because D2R agonists have antioxidant activity, we hypothesized that increased blood pressure in D2-/- is related to increased oxidative stress. D2-/- mice had increased urinary excretion of 8-isoprostane, a parameter of oxidative stress; increased activity of reduced nicotinamide-adenine dinucleotide phosphate oxidase in renal cortex; increased expression of the reduced nicotinamide-adenine dinucleotide phosphate oxidase subunits Nox1, Nox2, and Nox4; and decreased expression of the antioxidant enzyme heme-oxygenase-2 in the kidneys, suggesting that regulation of reactive oxygen species (ROS) production by D2R involves both pro-oxidant and antioxidant systems. Apocynin, a reduced nicotinamide-adenine dinucleotide phosphate oxidase inhibitor, or hemin, an inducer of heme oxigenase-1, normalized the blood pressure in D2-/- mice. Because D2Rs in the adrenal gland are implicated in aldosterone regulation, we evaluated whether alterations in aldosterone secretion contribute to ROS production in this model. Urinary aldosterone was increased in D2-/- mice and its response to a high-sodium diet was impaired. Spirolactone normalized the blood pressure in D2-/- mice and the renal expression of Nox1 and Nox4, indicating that the increased blood pressure and ROS production are, in part, mediated by impaired aldosterone regulation. However, spironolactone did not normalize the excretion of 8-isoprostane and had no effect on expression of Nox2 or heme-oxygenase-2. Our results show that the D2R is involved in the regulation of ROS production and that, by direct and indirect mechanisms, altered D2R function may result in ROS-dependent hypertension.

This document describes the collider layouts to be taken into account for further detailed studies. The optimization of the arc cell lattice and the choice made on the dispersion suppressor are explained. The arc lattice is detailed with the procedures to tune the collider ring and to correct the chromaticity. The correction schemes of the orbit, of the dynamic aperture and of the spurious dispersion are detailed. Finally, the properties of the arc design at the injection energy are shown.

To synthesize potent antagonists of the mu-opioid receptor, we prepared a series of endomorphin-1 and endomorphin-2 analogues with 3-(1-naphthyl)-d-alanine (d-1-Nal) or 3-(2-naphthyl)-d-alanine (d-2-Nal) in position 4. Some of these analogues displayed weak antagonist properties. We tried to strengthen these properties by introducing the structurally modified tyrosine residue 2,6-dimethyltyrosine (Dmt) in place of Tyr1. Among the synthesized compounds, [Dmt1, d-2-Nal4]endomorphin-1, designated antanal-1, and [Dmt1, d-2-Nal4]endomorphin-2, designated antanal-2, turned out to be highly potent and selective mu-opioid receptor antagonists, as judged on the basis of two functional assays, the receptor binding assay and the hot plate test of analgesia. Interestingly, another analogue of this series, [Dmt1, d-1-Nal4]endomorphin-1, turned out to be a moderately potent mixed mu-agonist/delta-antagonist.

A D2CS of a graph G is a set $S \\subseteq V(G)$ with $diam(G[S]) \\leq 2$. We study the problem of counting and enumerating D2CS of a graph. First we give an explicit formula for the number of D2CS in a complete k-ary tree, Fibonacci tree, binary Fibonacci tree and the binomial tree. Next we give an algorithm for enumerating and counting D2CS of a graph. We then give a linear time algorithm for finding all maximal D2CS in a strongly chordal graph.

We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C4...

Chapter 7 of a book on school law, this chapter deals with 1979 cases involving disputes over property. Cases involving taxpayer attempts to prevent the construction of school buildings dominate this year's property chapter, as they did last year's. Yet, paradoxically, there is also a significant increase in cases in which taxpayers tried to…

The assessment of the efficacy of dietary and supplemental vitamin D tends to be confounded by differences in the serum 25-hydroxyvitamin D response between vitamin D2 and vitamin D3. Serum response differences from these vitamers may be due to differences in bioavailability. To address this specifically, the bioaccessibility was assessed for vitamin D2 from breads fortified with UV-treated yeast, and a benchmark against staple vitamin D3 fortified foods including bovine milks and infant formula, as well as crystalline vitamin D2 fortified bread. Fortified foods were subjected to a three-stage static in vitro digestion model, and vitamin D was analyzed by HPLC-MS. Vitamin D bioaccessibility was significantly greater from bovine milks and infant formula (71-85%) than from yeast-fortified sandwich breads (6-7%). Bioaccessibility was not different between whole wheat and white wheat bread (p > 0.05), but was ∼4× lower from yeast-fortified bread than from crystalline vitamin D2 fortified bread (p D2 in comparison to other vitamin D2 sources is likely due to entrapment within a less digestible yeast matrix and not only to metabolic differences between vitamins D2 and D3.

Full Text Available Dopamine, through D2 receptor (D2R, is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L and short (D2S, are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850. SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process.

Our previous studies revealed that the double variants of CYP105A1- R73A/R84A and R73V/R84A-show high levels of activity with respect to conversion of vitamin D3 to its biologically active form, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study, we found that both the double variants were also capable of converting vitamin D2 to its active form, that is, 1α,25-dihydroxyvitamin D2 (1α,25(OH)2D2), via 25(OH)D2, whereas its 1α-hydroxylation activity toward 25(OH)D2 was much lower than that toward 25(OH)D3. Comparison of the wild type and the double variants revealed that the amino acid substitutions remarkably enhanced both 25- and 26-hydroxylation activity toward vitamin D2. After 25-hydroxylation of vitamin D2, further hydroxylation at C26 may occur frequently without the release of 25(OH)D2 from the substrate-binding pocket. Thus, the double variants of CYP105A1 are quite useful to produce 25,26(OH)2D2 that is one of the metabolites of vitamin D2 detected in human serum.

Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro. Blockade of D2DR with its antagonist (sulpiride and L-741,626, i.t.) attenuated morphine antinociceptive tolerance without affecting basal pain perception. Sulpiride (i.t.) also down-regulated the expression of phosphorylation of NR1, PKC, MAPKs and suppressed the activation of astrocytes and microglia induced by chronic morphine administration. Particularly, D2DR was found to interact with μ opioid receptor (MOR) in neurons, and chronic morphine treatment enhanced the MOR/D2DR interactions. Sulpiride (i.t.) could disrupt the MOR/D2DR interactions and attenuate morphine tolerance, indicating that neuronal D2DR in the spinal cord may be involved in morphine tolerance possibly by interacting with MOR. These results may present new opportunities for the treatment and management of morphine-induced antinociceptive tolerance which often observed in clinic. PMID:28004735

Glutamate receptor delta2 (GluD2) is selectively expressed on the postsynaptic spines at parallel-fiber (PF)-Purkinje neuron (PN) synapses. GluD2 knockout mice show a reduced number of PF-PN synapses, suggesting that GluD2 is involved in synapse formation. Recent studies revealed that GluD2 induces presynaptic differentiation in a manner dependent on its N-terminal domain (NTD) through binding of Cbln1 secreted from cerebellar granule neurons. However, the underlying mechanism of the specific binding of the NTD to Cbln1 remains elusive. Here, we have identified the flap loop (Arg321-Trp339) in the NTD of GluD2 (GluD2-NTD) as a crucial region for the binding to Cbln1 and the induction of presynaptic differentiation. Both induction of presynaptic differentiation and binding of Cbln1 were abolished in the HEK cells expressing not wild-type GluD2 but GluD2 with mutations in the flap loop. Especially, single amino acid substitution of either Arg321 or Trp323 to alanine was sufficient to disable the GluD2 function. Finally, a homology model of GluD2-NTD suggested that the flap loop is located at the distal end, which appears consistent with an interaction with Cbln1 and a presynaptic varicosity.

Diabetes results from an inadequate mass of functional beta cells, due to either beta cell loss caused by autoimmune destruction (Type I diabetes) or beta cell failure in response to insulin resistance (Type II diabetes). Elucidating the mechanisms that regulate beta cell mass may be key to developing new techniques that foster beta cell regeneration as a cellular therapy to treat diabetes. While previous studies concluded that cyclin D2 is required for postnatal beta cell self-renewal in mice, it is not clear if cyclin D2 is sufficient to drive beta cell self-renewal. Using transgenic mice that overexpress cyclin D2 specifically in beta cells, we show that cyclin D2 overexpression increases beta cell self-renewal post-weaning and results in increased beta cell mass. Beta cells that overexpress cyclin D2 are responsive to glucose stimulation, suggesting they are functionally mature. Beta cells that overexpress cyclin D2 demonstrate an enhanced regenerative capacity after injury induced by streptozotocin toxicity. To understand if cyclin D2 overexpression is sufficient to drive beta cell self-renewal, we generated a novel mouse model where cyclin D2 is only expressed in beta cells of cyclin D2(-/-) mice. Transgenic overexpression of cyclin D2 in cyclin D2(-)(/)(-) beta cells was sufficient to restore beta cell mass, maintain normoglycaemia, and improve regenerative capacity when compared to cyclin D2(-/-) littermates. Taken together, our results indicate that cyclin D2 is sufficient to regulate beta cell self-renewal and that manipulation of its expression could be used to enhance beta cell regeneration.

Dopamine (DA) is the most abundant catecholaminergic neurotransmitter in the brain.It controls a variety of physiological functions of the central nervous system by Dopamine receptor, and Dopamine D2 receptor has been associated with a variety of neuropathological diseases, such as drug addiction, schizophrenia. Parkinson's disease. But so Tar. the structure of Dopamine D2 receptor is not available, which limited the design and development of relevenl drugs in this paper, the homology model of Dopamine D2 receptor was developed by using the Dopamine D3 receptor (JPBL) as template, which has (he highest sequence identity to D2 receptor. After Optimization and molecular dynamics simulation, the refined model structure was obtained. The final refined model was assessed by Profile-3D and Ramachamlran plot programs, then verified by docking with stepholidine(SPD). The results show that the Dopamine D2 model which we built is reasonable and reliable.%多巴胺是大脑中含量最丰富的儿茶酚胺类神经递质,主要通过多巴胺受体调控中枢神经系统的多种生理功能,其中多巴胺D2受体与药物成瘾、精神分裂症、帕金森病等多种疾病的发生相关.然而多巴胺D2受体的晶体结构至今尚未解析出来,给相关疾病的药物设计与开发带来困难.本文采用同源模建的方法,用目前与多巴胺D2受体同源性最高的多巴胺D3受体(3PBL)作为模板,构建多巴胺D2受体的三维结构.经过优化和分子动力学模拟,用Profile-3D和Ramachandran plot对模型进行评估,然后用多巴胺D2受体拮抗剂千金藤啶碱(stepholidine,SPD)进行对接验证,证明构建的多巴胺D2受体模型合理、可靠.

Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.

The dopamine D2 receptor (D2R) is involved in food reward and compulsive food intake. The present study developed a virtual screening (VS) method to identify food components, which may modulate D2R signalling. In contrast to their common applications in drug discovery, VS methods are rarely applied for the discovery of bioactive food compounds. Here, databases were created that exclusively contain substances occurring in food and natural sources (about 13,000 different compounds in total) as the basis for combined pharmacophore searching, hit-list clustering and molecular docking into D2R homology models. From 17 compounds finally tested in radioligand assays to determine their binding affinities, seven were classified as hits (hit rate = 41%). Functional properties of the five most active compounds were further examined in β-arrestin recruitment and cAMP inhibition experiments. D2R-promoted G-protein activation was observed for hordenine, a constituent of barley and beer, with approximately identical ligand efficacy as dopamine (76%) and a Ki value of 13 μM. Moreover, hordenine antagonised D2-mediated β-arrestin recruitment indicating functional selectivity. Application of our databases provides new perspectives for the discovery of bioactive food constituents using VS methods. Based on its presence in beer, we suggest that hordenine significantly contributes to mood-elevating effects of beer.

We previously reported an association between the SH2D2A gene encoding TSAd and multiple sclerosis (MS). Here a total of 2128 Nordic MS patients and 2004 controls were genotyped for the SH2D2A promoter GA repeat polymorphism and rs926103 encoding a serine to asparagine substitution at amino acid...... that the SH2D2A gene may contribute to susceptibility to MS Udgivelsesdato: 2008/7/15...

The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…

Glutamate receptor delta2 (GluD2) is selectively expressed on the postsynaptic spines at parallel-fiber (PF)-Purkinje neuron (PN) synapses. GluD2 knockout mice show a reduced number of PF-PN synapses, suggesting that GluD2 is involved in synapse formation. Recent studies revealed that GluD2 induces presynaptic differentiation in a manner dependent on its N-terminal domain (NTD) through binding of Cbln1 secreted from cerebellar granule neurons. However, the underlying mechanism of the specific...

Full Text Available We examined the expression of cyclins D1, D2, D3, and E in mouse B-lymphocytic tumors. Cyclin D2 mRNA was consistently elevated in plasmacytomas, which characteristically contain Myc-activating chromosome translocations and constitutive c-Myc mRNA and protein expression. We examined the nature of cyclin D2 overexpression in plasmacytomas and other tumors. Human and mouse tumor cell lines that exhibited c-Myc dysregulation displayed instability of the cyclin D2 gene, detected by Southern blot, fluorescent in situ hybridization (FISH, and in extrachromosomal preparations (Hirt extracts. Cyclin D2 instability was not seen in cells with low levels of c-Myc protein. To unequivocally demonstrate a role of c-Myc in the instability of the cyclin D2 gene, a Myc-estrogen receptor chimera was activated in two mouse cell lines. After 3 to 4 days of Myc-ERTm activation, instability at the cyclin D2 locus was seen in the form of extrachromosomal elements, determined by FISH of metaphase and interphase nuclei and of purified extrachromosomal elements. At the same time points, Northern and Western blot analyses detected increased cyclin D2 mRNA and protein levels. These data suggest that Myc-induced genomic instability may contribute to neoplasia by increasing the levels of a cell cycle—regulating protein, cyclin D2, via intrachromosomal amplification of its gene or generation of extrachromosomal copies.

Full Text Available Abstract Sulforaphane (SFN, an isothiocyanate derived from cruciferous vegetables, induces potent anti-proliferative effects in prostate cancer cells. One mechanism that may contribute to the anti-proliferative effects of SFN is the modulation of epigenetic marks, such as inhibition of histone deacetylase (HDAC enzymes. However, the effects of SFN on other common epigenetic marks such as DNA methylation are understudied. Promoter hyper-methylation of cyclin D2, a major regulator of cell cycle, is correlated with prostate cancer progression, and restoration of cyclin D2 expression exerts anti-proliferative effects on LnCap prostate cancer cells. Our study aimed to investigate the effects of SFN on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells. We found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs, especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways. Our results demonstrated the ability of SFN to epigenetically modulate cyclin D2 expression, and provide novel insights into the mechanisms by which SFN may regulate gene expression as a prostate cancer chemopreventive agent.

Dopamine depletion in Parkinson's disease (PD) produces dendritic spine loss in striatal medium spiny neurons (MSNs) and increases their excitability. However, the synaptic changes that occur in MSNs in PD, in particular those induced by chronic L-3,4-dihydroxyphenylalanine (L-DOPA) treatment, are still poorly understood. We exposed BAC-transgenic D1-tomato and D2-eGFP mice to PD and dyskinesia model paradigms, enabling cell type-specific assessment of changes in synaptic physiology and morphology. The distinct fluorescence markers allowed us to identify D1 and D2 MSNs for analysis using intracellular sharp electrode recordings, electron microscopy, and 3D reconstructions with single-cell Lucifer Yellow injections. Dopamine depletion induced spine pruning in both types of MSNs, affecting mushroom and thin spines equally. Dopamine depletion also increased firing rate in both D1- and D2-MSNs, but reduced evoked-EPSP amplitude selectively in D2-MSNs. L-DOPA treatment that produced dyskinesia differentially affected synaptic properties in D1- and D2-MSNs. In D1-MSNs, spine density remained reduced but the remaining spines were enlarged, with bigger heads and larger postsynaptic densities. These morphological changes were accompanied by facilitation of action potential firing triggered by synaptic inputs. In contrast, although L-DOPA restored the number of spines in D2-MSNs, it resulted in shortened postsynaptic densities. These changes in D2-MSNs correlated with a decrease in synaptic transmission. Our findings indicate that L-DOPA-induced dyskinesia is associated with abnormal spine morphology, modified synaptic transmission, and altered EPSP-spike coupling, with distinct effects in D1- and D2-MSNs. PMID:27613437

We present a diagnostic analysis of the marine lowcloud climatology simulated by two state-of-the-art coupled atmosphere-ocean models: the NCAR Community Earth System Model (CESM) and the NCEP Global Forecasting System (GFS). In both models, the shallow convection and boundary layer turbulence parameterizations have been recently updated: both models now use a mass-flux scheme for the parameterization of shallow convection, and a turbulence parameterization capable of handling Stratocumulus (Sc)-topped Planetary Boundary Layers (PBLs). For shallow convection, both models employ a convective trigger function based on the concept of convective inhibition and both include explicit convective overshooting/penetrative entrainment formulation. For Sc-topped PBL, both models treat explicitly turbulence mixing and cloud-top entrainment driven by cloud-top radiative cooling. Our focus is on the climatological transition from Sc to shallow Cumulus (Cu)-topped PBL in the subtropical eastern oceans. We show that in the CESM the coastal Sc-topped PBLs in the subtropical Eastern Pacific are well-simulated but the climatological transition from Sc to shallow Cu is too abrupt and happens too close to the coast. By contrast, in the GFS coupled simulation the coastal Sc amount and PBL depth are severely underestimated while the transition from Sc to shallow Cu is ³delayed² and offshore Sc cover is too extensive in the subtropical Eastern Pacific. We discuss the possible connections between such differences in the simulations and differences in the parameterizations of shallow convection and boundary layer turbulence in the two models.

The formation of water (H2O) in the interstellar medium is intrinsically linked to grain-surface chemistry; thought to involve reactions between atomic (or molecular) hydrogen with atomic oxygen (O), molecular oxygen (O2), and ozone (O3). Laboratory precedent suggests that H2O is produced efficiently when O2 ices are exposed to H atoms (~100 K). This leads to the sequential generation of the hydroxyperoxyl radical (HO2), then hydrogen peroxide (H2O2), and finally H2O and a hydroxyl radical (OH); despite a barrier of ~2300 K for the last step. Recent detection of the four involved species toward ρ Oph A supports this general scenario; however, the precise formation mechanism remains undetermined. Here, solid O2 ice held at 12 K is exposed to a monoenergetic beam of 5 keV D+ ions. Products formed during the irradiation period are monitored through FTIR spectroscopy. O3 is observed through seven archetypal absorptions. Three additional bands found at 2583, 2707, and 1195 cm -1 correspond to matrix isolated DO2 (ν1) and D2O2 (ν1, ν5), and D2O (ν2), respectively. During subsequent warming, the O2 ice sublimates, revealing a broad band at 2472 cm-1 characteristic of amorphous D2O (ν1, ν3). Sublimating D2, D2O, D2O2, and O3 products were confirmed through their subsequent detection via quadrupole mass spectrometry. Reaction schemes based on both thermally accessible and suprathermally induced chemistries were developed to fit the observed temporal profiles are used to elucidate possible reaction pathways for the formation of D2-water. Several alternative schemes to the hydrogenation pathway (O2→HO2→H2O2→H2O) were identified; their astrophysical implications are briefly discussed.

Membrane levels of docosahexaenoic acid (DHA), an essential omega-3 polyunsaturated fatty acid (ω-3 PUFA), are decreased in common neuropsychiatric disorders. DHA modulates key cell membrane properties like fluidity, thereby affecting the behaviour of transmembrane proteins like G protein-coupled receptors (GPCRs). These receptors, which have special relevance for major neuropsychiatric disorders have recently been shown to form dimers or higher order oligomers, and evidence suggests that DHA levels affect GPCR function by modulating oligomerisation. In this study, we assessed the effect of membrane DHA content on the formation of a class of protein complexes with particular relevance for brain disease: adenosine A2A and dopamine D2 receptor oligomers. Using extensive multiscale computer modelling, we find a marked propensity of DHA for interaction with both A2A and D2 receptors, which leads to an increased rate of receptor oligomerisation. Bioluminescence resonance energy transfer (BRET) experiments performed on living cells suggest that this DHA effect on the oligomerisation of A2A and D2 receptors is purely kinetic. This work reveals for the first time that membrane ω-3 PUFAs play a key role in GPCR oligomerisation kinetics, which may have important implications for neuropsychiatric conditions like schizophrenia or Parkinson’s disease.

Full Text Available The low-temperature properties of systems characterized by a spontaneously broken internal rotation symmetry, O(N→O(N−1, are governed by Goldstone bosons and can be derived systematically within effective Lagrangian field theory. In the present study we consider systems living in two spatial dimensions, and evaluate their partition function at low temperatures and weak external fields up to three-loop order. Although our results are valid for any such system, here we use magnetic terminology, i.e., we refer to quantum spin systems. We discuss the sign of the (pseudo-Goldstone boson interaction in the pressure, staggered magnetization, and susceptibility as a function of an external staggered field for general N. As it turns out, the d=2+1 quantum XY model (N=2 and the d=2+1 Heisenberg antiferromagnet (N=3, are rather special, as they represent the only cases where the spin-wave interaction in the pressure is repulsive in the whole parameter regime where the effective expansion applies. Remarkably, the d=2+1 XY model is the only system where the interaction contribution in the staggered magnetization (susceptibility tends to positive (negative values at low temperatures and weak external field.

Previous works have shown that dressing of diatomic molecules by standing or by running laser waves gives rise to the appearance of so-called light-induced conical intersections (LICIs). Because of the strong nonadiabatic couplings, the existence of such LICIs may significantly change the dynamical properties of a molecular system. In our former paper (J. Phys. Chem. A 2013, 117, 8528), the photodissociation dynamics of the D(2)(+) molecule were studied in the LICI framework starting the initial vibrational nuclear wave packet from the superposition of all the vibrational states initially produced by ionizing D(2). The present work complements our previous investigation by letting the initial nuclear wave packets start from different individual vibrational levels of D(2)(+), in particular, above the energy of the LICI. The kinetic energy release spectra, the total dissociation probabilities, and the angular distributions of the photofragments are calculated and discussed. An interesting phenomenon has been found in the spectra of the photofragments. Applying the light-induced adiabatic picture supported by LICI, explanations are given for the unexpected structure of the spectra.

Plastid encoded genes of the dinoflagellates are rapidly evolving and most divergent. The importance of unusually accumulated mutations on structure of PSII core protein and photosynthetic function was examined in the dinoflagellates, Symbiodinium sp. and Alexandrium tamarense. Full-length cDNA sequences of psbA (D1 protein) and psbD (D2 protein) were obtained and compared with the other oxygen-evolving photoautotrophs. Twenty-three amino acid positions (7%) for the D1 protein and 34 positions (10%) for the D2 were mutated in the dinoflagellates, although amino acid residues at these positions were conserved in cyanobacteria, the other algae, and plant. Many mutations were likely to distribute in the N-terminus and the D-E interhelical loop of the D1 protein and helix B of D2 protein, while the remaining regions were well conserved. The different structural properties in these mutated regions were supported by hydropathy profiles. The chlorophyll fluorescence kinetics of the dinoflagellates was compared with Synechocystis sp. PCC6803 in relation to the altered protein structure.

Distinct populations of D1- and D2-dopamine receptor-expressing medium spiny neurons (D1-/D2-MSNs) comprise the nucleus accumbens, and activity in D1-MSNs promotes, whereas activity in D2-MSNs inhibits, motivated behaviors. We used chemogenetics to extend D1-/D2-MSN cell specific regulation to cue-reinstated cocaine seeking in a mouse model of self-administration and relapse, and found that either increasing activity in D1-MSNs or decreasing activity in D2-MSNs augmented cue-induced reinstatement. Both D1- and D2-MSNs provide substantial GABAergic innervation to the ventral pallidum, and chemogenetic inhibition of ventral pallidal neurons blocked the augmented reinstatement elicited by chemogenetic regulation of either D1- or D2-MSNs. Because D1- and D2-MSNs innervate overlapping populations of ventral pallidal neurons, we next used optogenetics to examine whether changes in synaptic plasticity in D1- versus D2-MSN GABAergic synapses in the ventral pallidum could explain the differential regulation of VP activity. In mice trained to self-administer cocaine, GABAergic LTD was abolished in D2-, but not in D1-MSN synapses. A μ opioid receptor antagonist restored GABA currents in D2-, but not D1-MSN synapses of cocaine-trained mice, indicating that increased enkephalin tone on presynaptic μ opioid receptors was responsible for occluding the LTD. These results identify a behavioral function for D1-MSN innervation of the ventral pallidum, and suggest that losing LTDGABA in D2-MSN, but not D1-MSN input to ventral pallidum may promote cue-induced reinstatement of cocaine-seeking. More than 90% of ventral striatum is composed of two cell types, those expressing dopamine D1 or D2 receptors, which exert opposing roles on motivated behavior. Both cell types send GABAergic projections to the ventral pallidum and were found to differentially promote cue-induced reinstatement of cocaine seeking via the ventral pallidum. Furthermore, after cocaine self-administration, synaptic

The principle neurons of the striatum are GABAergic medium spiny neurons (MSNs), whose collateral synapses onto neighboring neurons play critical roles in striatal function. MSNs can be divided by dopamine receptor expression into D1-class and D2-class MSNs, and alterations in D2 MSNs are associated with various pathological states. Despite overwhelming evidence for D2 receptors (D2Rs) in maintaining proper striatal function, it remains unclear how MSN collaterals are specifically altered by D2R activation. Here, we report that chronic D2R stimulation regulates MSN collaterals in vitro by presynaptic and postsynaptic mechanisms. We used corticostriatal cultures from mice in which MSN subtypes were distinguished by fluorophore expression. Quinpirole, an agonist for D2/3 receptors, was used to chronically activate D2Rs. Quinpirole increased the rate and strength of collateral formation onto D2R-containing MSNs as measured by dual whole-cell patch-clamp recordings. Additionally, these neurons were more sensitive to low concentrations of GABA and exhibited an increase in gephyrin puncta density, suggesting increased postsynaptic GABAA receptors. Last, quinpirole treatment increased presynaptic GABA release sites, as shown by increased frequency of sIPSCs and mIPSCs, correlating with increased VGAT (vesicular GABA transporter) puncta. Combined with the observation that there were no detectable differences in sensitivity to specific GABAA receptor modulators, we provide evidence that D2R activation powerfully transforms MSN collaterals via coordinated presynaptic and postsynaptic alterations. As the D2 class of MSNs is highly implicated in Parkinson's disease and other neurological disorders, our findings may contribute to understanding and treating the changes that occur in these pathological states. PMID:23986243

Options for chronic treatment of hypoparathyroidism include calcitriol, recombinant human parathyroid hormone, and high-dose vitamin D (D2). D2 is used in a minority of patients because of fear of prolonged hypercalcemia and renal toxicity. There is a paucity of recent data about D2 use in hypoparathyroidism. Compare renal function, hypercalcemia, and hypocalcemia in patients with hypoparathyroidism treated chronically with either D2 (D2 group) or calcitriol. A retrospective study of patients with hypoparathyroidism treated at the University of Maryland Hospital. Participants were identified by a billing record search with diagnosis confirmed by chart review. Thirty patients were identified; 16 were treated chronically with D2, 14 with calcitriol. Data were extracted from medical records. Serum creatinine and calcium, hospitalizations, and emergency department (ED) visits for hypercalcemia and hypocalcemia. D2 and calcitriol groups were similar in age (58.9 ± 16.7 vs 50.9 ± 22.6 years, P = 0.28), sex, and treatment duration (17.8 ± 14.2 vs 8.5 ± 4.4 years, P = 0.076). Hospitalization or ED visits for hypocalcemia occurred in none of the D2 group vs four of 14 in the calcitriol group (P = 0.03); three in the calcitriol group had multiple ED visits. There were no differences between D2 and calcitriol groups in hospitalizations or ED visits for hypercalcemia, serum creatinine or calcium, or kidney stones. We found less morbidity from hypocalcemia in hypoparathyroid patients treated chronically with D2 compared with calcitriol and found no difference in renal function or morbidity from hypercalcemia. Treatment with D2 should be considered in patients with hypoparathyroidism, particularly in those who experience recurrent hypocalcemia.

The Arabidopsis mutant shm1-1 is defective in mitochondrial serine hydroxymethyltransferase 1 activity and displays a lethal photorespiratory phenotype at ambient CO2 concentration but grows normally at high CO2 . After transferring high CO2 -grown shm1-1 plants to ambient CO2 , the younger leaves remain photosynthetically active while developed leaves display increased yellowing and decreased FV /FM values. Metabolite analysis of plants transferred from high CO2 to ambient air indicates a massive light-dependent (photorespiratory) accumulation of glycine, 2-oxoglutarate (2OG) and D-2-hydroxyglutarate (D-2HG). Amino acid markers of senescence accumulated in ambient air in wild-type and shm1-1 plants maintained in darkness and also build up in shm1-1 in the light. This, together with an enhanced transcription of the senescence marker SAG12 in shm1-1, suggests the initiation of senescence in shm1-1 under photorespiratory conditions. Mitochondrial D-2HG dehydrogenase (D-2HGDH) converts D-2HG into 2OG. In vitro studies indicate that 2OG exerts competitive inhibition on D-2HGDH with a Ki of 1.96 mm. 2OG is therefore a suitable candidate as inhibitor of the in vivo D-2HGDH activity, as 2OG is produced and accumulates in mitochondria. Inhibition of the D-2HGDH by 2OG is likely a mechanism by which D-2HG accumulates in shm1-1, however it cannot be ruled out that D-2HG may also accumulate due to an active senescence programme that is initiated in these plants after transfer to photorespiratory conditions. Thus, a novel interaction of the photorespiratory pathway with cellular processes involving D-2HG has been identified.

Intensification of manufacturing processes and expansion of usability envelopes of modern components and structures in many cases result in dynamic loading regimes that cannot be resented adequately employing quasi-static formulations of respective problems of solid mechanics. Specific features of dynamic deformation, damage and fracture processes are linked to various factors, most important among them being: a transient character of load application; complex scenarios of propagation, attenuation and reflection of stress waves in real materials, components and structures; strain-rate sensitivity of materials properties; various thermo-mechanical regimes. All these factors make both experimental characterisation and theoretical (analytical and numerical) analysis of dynamic deformation and fracture rather challenging; for instance, besides dealing with a spatial realisation of these processes, their evolution with time should be also accounted for. To meet these challenges, an International Symposium on Dynamic Deformation and Fracture of Advanced Materials D2FAM 2013 was held on 9-11 September 2013 in Loughborough, UK. Its aim was to bring together specialists in mechanics of materials, applied mathematics, physics, continuum mechanics, materials science as well as various areas of engineering to discuss advances in experimental and theoretical analysis, and numerical simulations of dynamic mechanical phenomena. Some 50 papers presented at the Symposium by researchers from 12 countries covered various topics including: high-strain-rate loading and deformation; dynamic fracture; impact and blast loading; high-speed penetration; impact fatigue; damping properties of advanced materials; thermomechanics of dynamic loading; stress waves in micro-structured materials; simulation of failure mechanisms and damage accumulation; processes in materials under dynamic loading; a response of components and structures to harsh environment. The materials discussed at D2FAM 2013

Full Text Available Vitamin D is a lipid soluble steroid hormone with pleiotropic biological properties, including regulation of cell proliferation, differentiation and apoptosis. As to these desirable anticancer actions, 1,25-dihydroxyvitamins D and analogs have been reported to inhibit the proliferation and to induce differentiation of a wide variety of cancer cell types, including human malignant melanoma. However, there is a need for novel and more efficacious vitamin D analogs, and how best to design such is still an open issue. A series of double point modified (DPM analogs of 1,25-dihydroxyvitamin D2 (1,25(OH2D2 induced differentiation of the vitamin D receptor (VDR positive A375 and VDR negative SK-MEL 188b human malignant melanoma cell lines. Surprisingly, the dose of 1,25(OH2D2 required to inhibit the proliferation of the A375 melanoma cell line by was several fold lower than that required in the case of 1,25(OH2D3. To evaluate the impact of the modification in the side chain (additional 22-hydroxyl and in the A-ring (5,6-trans modification, the regular side-chain of vitamin D2 or D3 was retained in the structure of our analogs. As expected, 5,6-trans modification was advantageous to enhancing the anti-proliferative activity of analogs, but not as a single point modification (SPM. Very unexpectedly, the additional 22-hydroxyl in the side-chain reduced significantly the anti-proliferative activity of both the natural and 5,6-trans series analogs. Finally, an induction of pigmentation in melanoma SK-MEL 188b cells was observed to sensitized cells to the effect of vitamin D analogs.

Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.

In Cebus albifrons monkeys it was demonstrated that vitamin D(3) promotes the intestinal absorption of calcium-47 and that vitamin D(2) does not increase absorption above that seen in monkeys deficient in vitamin D. These data support previous observations that vitamin D(2) is not effective in preventing metabolic bone disease in this species.

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area

Patients with malignant gliomas have a poor prognosis with average survival of less than 1 year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite that was discovered first in this tumor entity. D2HG is generated in large amounts due to various "gain-of-function" mutations in the isocitrate dehydrogenases IDH1 and IDH2. Meanwhile, D2HG has been detected in several other tumor entities, including intrahepatic bile-duct cancer, chondrosarcoma, acute myeloid leukemia, and angioimmunoblastic T-cell lymphoma. D2HG is barely detectable in healthy tissue (bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography/mass spectrometry. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0-10 μmol/g tissue (wet weight). In combination with the already established bioluminescence imaging techniques for ATP, glucose, pyruvate, and lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual tumors in a further dimension.

In several experimental techniques D2O rather then H2O is often used as a solvent for proteins. Concerning the influence of the solvent on the stability of the proteins, contradicting results have been reported in literature. In this paper the influence of H2O-D2O solvent substitution on the stabili

Dopamine D2 receptors (D2R) play a major role in cognition, mood and motor movements. Their blockade by antipsychotic drugs reduces hallucinatory and delusional behaviors in schizophrenia, but often fails to alleviate affective and cognitive dysfunctions. The prefrontal cortex (PFC) expresses D2R and is altered in schizophrenia. We investigated how D2R modulate behavior and PFC function in monkeys. Two monkeys learned new and performed highly familiar visuomotor associations, where each cue was associated with a saccade to a right or left target. We recorded neural spikes and local field potentials from multiple electrodes while injecting the D2R antagonist eticlopride in the lateral PFC. Blocking prefrontal D2R impaired associative learning and cognitive flexibility, reduced motivation, but left the performance of familiar associations intact. Eticlopride reduced saccade-direction selectivity of prefrontal neurons, leading to a decrease in neural information about the associations, and an increase in alpha oscillations. These results, together with our recent study using a D1R antagonist, suggest that D1R and D2R in the primate lateral PFC cooperate to modulate several executive functions. Our findings help to gain insight into why antipsychotic drugs, with strong antagonistic actions on D2R, fail to ameliorate cognitive and emotional deficits in schizophrenia.

In several experimental techniques D2O rather then H2O is often used as a solvent for proteins. Concerning the influence of the solvent on the stability of the proteins, contradicting results have been reported in literature. In this paper the influence of H2O-D2O solvent substitution on the

In several experimental techniques D2O rather then H2O is often used as a solvent for proteins. Concerning the influence of the solvent on the stability of the proteins, contradicting results have been reported in literature. In this paper the influence of H2O-D2O solvent substitution on the

Full Text Available Several studies demonstrated improvement of depressive symptoms in treatment resistant depression (TRD after administering dopamine agonists which suggest abnormal dopaminergic neurotransmission in TRD. However, the role of dopaminergic signaling through measurement of striatal dopamine D(2/3 receptor (D2/3R binding has not been investigated in TRD subjects. We used [(123I]IBZM single photon emission computed tomography (SPECT to investigate striatal D2/3R binding in TRD. We included 6 severe TRD patients, 11 severe TRD patients on antipsychotics (TRD AP group and 15 matched healthy controls. Results showed no significant difference (p = 0.75 in striatal D2/3R availability was found between TRD patients and healthy controls. In the TRD AP group D2/3R availability was significantly decreased (reflecting occupancy of D2/3Rs by antipsychotics relative to TRD patients and healthy controls (p<0.001 but there were no differences in clinical symptoms between TRD AP and TRD patients. This preliminary study therefore does not provide evidence for large differences in D2/3 availability in severe TRD patients and suggests this TRD subgroup is not characterized by altered dopaminergic transmission. Atypical antipsychotics appear to have no clinical benefit in severe TRD patients who remain depressed, despite their strong occupancy of D2/3Rs.

We have investigated D^{+}\\pi^{-} and D^{*+}\\pi^{-} final states and observed the two established L=1 charmed mesons, the D_1(2420)^0 with mass 2421^{+1+2}_{-2-2} MeV/c^{2} and width 20^{+6+3}_{-5-3} MeV/c^{2} and the D_2^*(2460)^0 with mass 2465 \\pm 3 \\pm 3 MeV/c^{2} and width 28^{+8+6}_{-7-6} MeV/c^{2}. Properties of these final states, including their decay angular distributions and spin-parity assignments, have been studied. We identify these two mesons as the j_{light}=3/2 doublet predicted by HQET. We also obtain constraints on {\\footnotesize \\Gamma_S/(\\Gamma_S + \\Gamma_D)} as a function of the cosine of the relative phase of the two amplitudes in the D_1(2420)^0 decay. hardcopies with figures can be obtained by writing to: Pam Morehouse preprint secretary Newman Lab Cornell University Ithaca, NY 14853 or by sending mail to: preprints@lns62.lns.cornell.edu

We discuss a concept of particle localization which is motivated from quantum field theory, and has been proposed by Brunetti, Guido and Longo and by Schroer. It endows the single particle Hilbert space with a family of real subspaces indexed by the space-time regions, with certain specific properties reflecting the principles of locality and covariance. We show by construction that such a localization structure exists also in the case of massive anyons in d=2+1, i.e. for particles with positive mass and with arbitrary spin s in the reals. The construction is completely intrinsic to the corresponding ray representation of the (proper orthochronous) Poincare group. Our result is of particular interest since there are no free fields for anyons, which would fix a localization structure in a straightforward way. We present explicit formulas for the real subspaces, expected to turn out useful for the construction of a quantum field theory for anyons. In accord with well-known results, only localization in string-l...

Previous research demonstrates that Slc6a15, a neutral amino acid transporter, is associated with depression susceptibility. However, no study examined Slc6a15 in the ventral striatum [nucleus accumbens (NAc)] in depression. Given our previous characterization of Slc6a15 as a striatal dopamine receptor 2 (D2)-neuron-enriched gene, we examined the role of Slc6a15 in NAc D2-neurons in mediating susceptibility to stress in male mice. First, we showed that Slc6a15 mRNA was reduced in NAc of mice susceptible to chronic social defeat stress (CSDS), a paradigm that produces behavioral and molecular adaptations that resemble clinical depression. Consistent with our preclinical data, we observed Slc6a15 mRNA reduction in NAc of individuals with major depressive disorder (MDD). The Slc6a15 reduction in NAc occurred selectively in D2-neurons. Next, we used Cre-inducible viruses combined with D2-Cre mice to reduce or overexpress Slc6a15 in NAc D2-neurons. Slc6a15 reduction in D2-neurons caused enhanced susceptibility to a subthreshold social defeat stress (SSDS) as observed by reduced social interaction, while a reduction in social interaction following CSDS was not observed when Slc6a15 expression in D2-neurons was restored. Finally, since both D2-medium spiny neurons (MSNs) and D2-expressing choline acetyltransferase (ChAT) interneurons express Slc6a15, we examined Slc6a15 protein in these interneurons after CSDS. Slc6a15 protein was unaltered in ChAT interneurons. Consistent with this, reducing Slc5a15 selectively in NAc D2-MSNs, using A2A-Cre mice that express Cre selectively in D2-MSNs, caused enhanced susceptibility to SSDS. Collectively, our data demonstrate that reduced Slc6a15 in NAc occurs in MDD individuals and that Slc6a15 reduction in NAc D2-neurons underlies stress susceptibility.SIGNIFICANCE STATEMENT Our study demonstrates a role for reduced Slc6a15, a neutral amino acid transporter, in nucleus accumbens (NAc) in depression and stress susceptibility. The

Activation of KCNQ potassium channels by stimulation of co-expressed dopamine D(2) receptors was studied electrophysiologically in Xenopus laevis oocytes and in mammalian cells. To address the specificity of the interaction between D(2)-like receptors and KCNQ channels, combinations of KCNQ1...... activation of the KCNQ channels was confirmed by co-expression of other neuronal K(+) channels (BK, K(V)1.1, and K(V)4.3) with the D(2L) receptor in Xenopus oocytes. None of these K(+) channels responded to stimulation of the D(2L) receptor. In the mammalian brain, dopamine D(2) receptors and KCNQ channels...... co-localise postsynaptically in several brain regions, so modulation of neuronal excitability by dopamine release could in part be mediated via an effect on KCNQ channels....

All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role. We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound. We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates. PMID:22563388

Proteins that bind to G protein-coupled receptors have recently been identified as regulators of receptor anchoring and signaling. In this study, actin-binding protein 280 (ABP-280), a widely expressed cytoskeleton-associated protein that plays an important role in regulating cell morphology and motility, was found to associate with the third cytoplasmic loop of dopamine D(2) receptors. The specificity of this interaction was originally identified in a yeast two-hybrid screen and confirmed by protein binding. The functional significance of the D(2) receptor-ABP-280 association was evaluated in human melanoma cells lacking ABP-280. D(2) receptor agonists were less potent in inhibiting forskolin-stimulated cAMP production in these cells. Maximal inhibitory responses of D(2) receptor activation were also reduced. Further yeast two-hybrid experiments showed that ABP-280 association is critically dependent on the carboxyl domain of the D(2) receptor third cytoplasmic loop, where there is a potential serine phosphorylation site (S358). Serine 358 was replaced with aspartic acid to mimic the effects of receptor phosphorylation. This mutant (D(2)S358D) displayed compromised binding to ABP-280 and coupling to adenylate cyclase. PKC activation also generated D(2) receptor signaling attenuation, but only in ABP-containing cells, suggesting a PKC regulatory role in D(2)-ABP association. A mechanism for these results may be derived from a role of ABP-280 in the clustering of D(2) receptors, as determined by immunocytochemical analysis in ABP-deficient and replete cells. Our results suggest a new molecular mechanism of modulating D(2) receptor signaling by cytoskeletal protein interaction.

Tctex1d2 (Tctex1 domain containing 2) is an open reading frame that encodes for a functionally unknown protein that contains a Tctex1 domain found in dynein light chain family members. Examination of gene expression during adipogenesis demonstrated a marked increase in Tctex1d2 protein expression that was essentially undetectable in preadipocytes and markedly induced during 3T3-L1 adipocyte differentiation. Tctex1d2 overexpression significantly inhibited insulin-stimulated glucose transporter 4 (GLUT4) translocation and 2-deoxyglucose uptake. In contrast, Tctex1d2 knockdown significantly increased insulin-stimulated GLUT4 translocation and 2-deoxyglucose uptake. However, acute insulin stimulation (up to 30 min) in 3T3-L1 adipocytes with overexpression or knockdown of Tctex1d2 had no effect on Akt phosphorylation, a critical signal transduction target required for GLUT4 translocation. Although overexpression of Tctex1d2 had no significant effect on GLUT4 internalization, Tctex1d2 was found to associate with syntaxin 4 in an insulin-dependent manner and inhibit Doc2b binding to syntaxin 4. In addition, glucose-dependent insulinotropic polypeptide rescued the Tctex1d2 inhibition of insulin-stimulated GLUT4 translocation by suppressing the Tctex1d2-syntaxin 4 interaction and increasing Doc2b-Synatxin4 interactions. Taking these results together, we hypothesized that Tctex1d2 is a novel syntaxin 4 binding protein that functions as a negative regulator of GLUT4 plasma membrane translocation through inhibition of the Doc2b-syntaxin 4 interaction.

BACKGROUND AND PURPOSE Functional roles of the N-terminal region of rhodopsin-like GPCR family remain unclear. Using dopamine D2 and D3 receptors as a model system, we probed the roles of the N-terminal region in the signalling, intracellular trafficking of receptor proteins, and explored the critical factors that determine the functionality of the N-terminal region. EXPERIMENTAL APPROACH The N-terminal region of the D2 receptor was gradually shortened or switched with that of the D3 receptor or a non-specific sequence (FLAG), or potential N-terminal glycosylation sites were mutated. Effects of these manipulations on surface expression, internalization, post-endocytic behaviours and signalling were determined. KEY RESULTS Shortening the N-terminal region of the D2 receptor enhanced receptor internalization and impaired surface expression and signalling; ligand binding, desensitization and down-regulation were not affected but their association with a particular microdomain, caveolae, was disrupted. Replacement of critical residues within the N-terminal region with the FLAG epitope failed to restore surface expression but partially restored the altered internalization and signalling. When the N-terminal regions were switched between D2 and D3 receptors, cell surface expression pattern of each receptor was switched. Mutations of potential N-terminal glycosylation sites inhibited surface expression but enhanced internalization of D2 receptors. CONCLUSIONS AND IMPLICATIONS Shortening of N-terminus or mutation of glycosylation sites located within the N-terminus enhanced receptor internalization but impaired the surface expression of D2 receptors. The N-terminal region of the D2 receptor, in a sequence-specific manner, controls the receptor's conformation and integration into the plasma membrane, which determine its subcellular localization, intracellular trafficking and signalling properties. PMID:22117524

... to Food for Human Consumption; Vitamin D2 Bakers Yeast AGENCY: Food and Drug Administration, HHS... regulations to provide for the safe use of vitamin D2 bakers yeast as a source of vitamin D2 and as a... vitamin D2 per 100 grams (g) in the finished food. This action is in response to a petition filed...

A series of 2-aminotetralins, substituted with a methoxy or a hydroxy group on the 5- or 7-position, and with varying N-alkyl or N-arylalkyl substituents, were prepared and evaluated in binding assays for human dopamine (DA) D-2, D-3, and D-4 receptors. Some members of this series were prepared in f

Whereas dopamine agonists are known to provide symptomatic benefits for Parkinson's disease, recent clinical trials suggest that they might also be neuroprotective. Laboratory studies demonstrate that dopamine agonists can provide neuroprotective effects in a number of model systems, but the role of receptor-mediated signalling in these effects is controversial. We find that dopamine agonists have robust, concentration-dependent anti-apoptotic activity in PC12 cells that stably express human D(2L) receptors from cell death due to H(2)O(2) or trophic withdrawal and that the protective effects are abolished in the presence of D(2)-receptor antagonists. D(2) agonists are also neuroprotective in the nigral dopamine cell line SN4741, which express endogenous D(2) receptors, whereas no anti-apoptotic activity is observed in native PC12 cells, which do not express detectable D(2) receptors. Notably, the agonists studied differ in their relative efficacy to mediate anti-apoptotic effects and in their capacity to stimulate [(35)S]guanosine 5'-[gamma-thio]triphosphate ([(35)S]GTP[S]) binding, an indicator of G-protein activation. Studies with inhibitors of phosphoinositide 3-kinase (PI 3-kinase), extracellular-signal-regulated kinase or p38 mitogen-activated protein kinase indicate that the PI 3-kinase pathway is required for D(2) receptor-mediated cell survival. These studies indicate that certain dopamine agonists can complex with D(2) receptors to preferentially transactivate neuroprotective signalling pathways and to mediate increased cell survival.

The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

Strong mass signals of H-2 and D-2 ions have been observed from low-pressure dielectric barrier discharge hydrogen and deuterium plasmas via molecular beam mass spectrometry. The observed H-2/H- and D-2/D- ratios (~0.35-0.4) are over five orders of magnitude higher than those observed by other techniques. The kinetic energy of H-2 and D-2 ions sampled from the plasmas was determined to be widely distributed, from a few eV to >100 eV, giving lifetimes greater than ~40 µs for H-2 and ~55 µs for D-2. The highest vib-rotational excitation of neutral H2 species in the plasma was determined to be about J = 0, v = 5 or J = 19, v = 0 via threshold ionization mass spectrometry. The possible pumping mechanisms for generating H-2 with further high J, required by the current high-rotation model, have been proposed. Similar to the lifetime of D-2 determined recently by another group, the H-2 lifetime observed in this work is about two orders of magnitude longer than that predicted by the current theoretical model. To explain these experimental observations regarding the meta-stability of long-lived H-2 and D-2 ions, the improved current high-rotation model or other new models, including the possible existence of some long-lived electronically excited states of H-2/D-2, need to be developed.

Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects. PMID:27754480

Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.

This report presents a neutronics analysis of tight-pitch D2O-cooled PWRs loaded with MOX fuel and focuses essentially on the Pu breeding potential of such reactors as well as on an important safety parameter, the void coefficient, which has to be negative. It is well known that fast reactors have a better neutron economy and are better suited than thermal reactors to breed fissile material from neutron capture in fertile material. Such fast reactors (e.g. sodium-cooled reactors) usually rely on technologies that are very different from those of existing water-cooled reactors and are probably more expensive. This report investigates another possibility to obtain a fast neutron reactor while still relying mostly on a PWR technology by: (1) Tightening the lattice pitch to reduce the water-to-fuel volume ratio compared to that of a standard PWR. Water-to-fuel volume ratios of between 0.45 and 1 have been considered in this study while a value of about 2 is typical of standard PWRs, (2) Using D2O instead of H2O as a coolant. Indeed, because of its different neutron physics properties, the use of D2O hardens the neutron spectrum to an extent impossible with H2O when used in a tight-pitch lattice. The neutron spectra thus obtained are not as fast as those in sodium-cooled reactor but they can still be characterized as fast compared to that of standard PWR neutron spectra. In the phase space investigated in this study we did not find any configurations that would have, at the same time, a positive Pu mass balance (more Pu at the end than at the beginning of the irradiation) and a negative void coefficient. At this stage, the use of radial blankets has only been briefly addressed whereas the impact of axial blankets has been well defined. For example, with a D2O-to-fuel volume ratio of 0.45 and a core driver height of about 60 cm, the fissile Pu mass balance between the fresh fuel and the irradiated fuel (50 GWd/t) would be about -7.5% (i.e. there are 7.5% fewer fissile Pu

两条生物序列间的相似性比对是计算生物学探讨的主要问题之一,一种快速的依赖于k-元组的D2shepp统计法目前已被应用到非序列比对中.文中在零模型的基础上产生两条相互独立的随机序列,基于D2shepp统计法进行了两条序列的局部比对,找到局部比对的最优值并求和.在此基础上模拟了Power值的分布情况,并分析了不同k参数下的Power值分布.在相同参数下将文中提出的局部比对与已有的D2shepp统计的全局比对进行比较,发现局部比对D2shepp统计的Power值随着序列长度的增大而快速地接近于1,比全局比对更加快速、准确.%The similarities between two biological sequences is a major issue in computational biology, and a fast D2shepp statistics method based on the joint i-tuple content in two sequences has been used in the alignment-free sequence comparison. In this paper, two separate random sequences are generated based on the zero model, and their local alignment is conducted based on D2shepp statistics, thus obtaining the optimal values and the sum of these values. Then, the Power distribution is simulated and the distributions with different k values are analyzed. Finally, with the same parameters, the proposed local alignment is compared with the global alignment based on D2shepp statistics. It is found that the Power value of the proposed local alignment rapidly approaches 1 with the increase of the sequence length and that the proposed local alignment is quicker and more accurate than the global one.

Full Text Available In basal ganglia a significant subset of GABAergic medium spiny neurons (MSNs coexpress D1 and D2 receptors (D1R and D2R along with the neuropeptides dynorphin (DYN and enkephalin (ENK. These coexpressing neurons have been recently shown to have a region-specific distribution throughout the mesolimbic and basal ganglia circuits. While the functional relevance of these MSNs remains relatively unexplored, they have been shown to exhibit the unique property of expressing the dopamine D1-D2 receptor heteromer, a novel receptor complex with distinct pharmacology and cell signaling properties. Here we showed that MSNs coexpressing the D1R and D2R also exhibited a dual GABA/glutamate phenotype. Activation of the D1R-D2R heteromer in these neurons resulted in the simultaneous, but differential regulation of proteins involved in GABA and glutamate production or vesicular uptake in the nucleus accumbens (NAc, ventral tegmental area (VTA, caudate putamen and substantia nigra (SN. Additionally, activation of the D1R-D2R heteromer in NAc shell, but not NAc core, differentially altered protein expression in VTA and SN, regions rich in dopamine cell bodies. The identification of a MSN with dual inhibitory and excitatory intrinsic functions provides new insights into the neuroanatomy of the basal ganglia and demonstrates a novel source of glutamate in this circuit. Furthermore, the demonstration of a dopamine receptor complex with the potential to differentially regulate the expression of proteins directly involved in GABAergic inhibitory or glutamatergic excitatory activation in VTA and SN may potentially provide new insights into the regulation of dopamine neuron activity. This could have broad implications in understanding how dysregulation of neurotransmission within basal ganglia contributes to dopamine neuronal dysfunction.

Renal dopamine receptors participate in the regulation of blood pressure. Genetic factors, including polymorphisms of the dopamine D(2) receptor gene (DRD2) are associated with essential hypertension, but the mechanisms of their contribution are incompletely understood. Mice lacking Drd2 (D(2)-/-) have elevated blood pressure, increased renal expression of inflammatory factors, and renal injury. We tested the hypothesis that decreased dopamine D(2) receptor (D(2)R) function increases vulnerability to renal inflammation independently of blood pressure, is an immediate cause of renal injury, and contributes to the subsequent development of hypertension. In D(2)-/- mice, treatment with apocynin normalized blood pressure and decreased oxidative stress, but did not affect the expression of inflammatory factors. In mouse RPTCs Drd2 silencing increased the expression of TNFα and MCP-1, while treatment with a D(2)R agonist abolished the angiotensin II-induced increase in TNF-α and MCP-1. In uni-nephrectomized wild-type mice, selective Drd2 silencing by subcapsular infusion of Drd2 siRNA into the remaining kidney produced the same increase in renal cytokines/chemokines that occurs after Drd2 deletion, increased the expression of markers of renal injury, and increased blood pressure. Moreover, in mice with two intact kidneys, short-term Drd2 silencing in one kidney, leaving the other kidney undisturbed, induced inflammatory factors and markers of renal injury in the treated kidney without increasing blood pressure. Our results demonstrate that the impact of decreased D(2)R function on renal inflammation is a primary effect, not necessarily associated with enhanced oxidant activity, or blood pressure; renal damage is the cause, not the result, of hypertension. Deficient renal D(2)R function may be of clinical relevance since common polymorphisms of the human DRD2 gene result in decreased D(2)R expression and function.

Full Text Available Renal dopamine receptors participate in the regulation of blood pressure. Genetic factors, including polymorphisms of the dopamine D(2 receptor gene (DRD2 are associated with essential hypertension, but the mechanisms of their contribution are incompletely understood. Mice lacking Drd2 (D(2-/- have elevated blood pressure, increased renal expression of inflammatory factors, and renal injury. We tested the hypothesis that decreased dopamine D(2 receptor (D(2R function increases vulnerability to renal inflammation independently of blood pressure, is an immediate cause of renal injury, and contributes to the subsequent development of hypertension. In D(2-/- mice, treatment with apocynin normalized blood pressure and decreased oxidative stress, but did not affect the expression of inflammatory factors. In mouse RPTCs Drd2 silencing increased the expression of TNFα and MCP-1, while treatment with a D(2R agonist abolished the angiotensin II-induced increase in TNF-α and MCP-1. In uni-nephrectomized wild-type mice, selective Drd2 silencing by subcapsular infusion of Drd2 siRNA into the remaining kidney produced the same increase in renal cytokines/chemokines that occurs after Drd2 deletion, increased the expression of markers of renal injury, and increased blood pressure. Moreover, in mice with two intact kidneys, short-term Drd2 silencing in one kidney, leaving the other kidney undisturbed, induced inflammatory factors and markers of renal injury in the treated kidney without increasing blood pressure. Our results demonstrate that the impact of decreased D(2R function on renal inflammation is a primary effect, not necessarily associated with enhanced oxidant activity, or blood pressure; renal damage is the cause, not the result, of hypertension. Deficient renal D(2R function may be of clinical relevance since common polymorphisms of the human DRD2 gene result in decreased D(2R expression and function.

Although hyperprolactinemia carries a long-term risk of morbidity, the threshold of dopamine D2/3 receptor (D2/3R) occupancy for hyperprolactinemia has not been investigated in older patients with schizophrenia. Data were taken from a positron emission tomography (PET) study conducted between August 2007 and August 2015. The present post hoc study included 42 clinically stable outpatients with schizophrenia (DSM-IV) (mean ± SD age = 60.2 ± 6.7 years) taking olanzapine or risperidone. Subjects underwent [¹¹C]-raclopride PET scans to measure D2/3R occupancy before and after reducing their dose of antipsychotic by up to 40%. Blood samples were collected before each PET scan to measure prolactin levels. The relationship between prolactin levels and D2/3R occupancy was examined using stepwise linear regression analyses. The D2/3R occupancy thresholds for hyperprolactinemia were explored using Fisher exact tests. Prolactin levels decreased following dose reduction (mean ± SD = 24.1 ± 30.2 ng/mL to 17.2 ± 15.1 ng/mL; P D2/3R occupancy (β = .23, P = .04). Those with D2/3R occupancy of 66% or higher were more likely to have hyperprolactinemia than those with D2/3R occupancy lower than 66% (P = .03). Sensitivity, specificity, positive predictive value, and negative predictive value of this threshold were 0.44, 0.81, 0.78, and 0.48, respectively. We identified a D2/3R occupancy threshold for hyperprolactinemia of 66% in older patients with schizophrenia, which is lower than that reported in younger patients (73%) by other researchers. Our results suggest a higher sensitivity to antipsychotics in older patients. Prolactin levels could assist in the determination of appropriate antipsychotic dosing to minimize adverse effects. ClinicalTrials.gov identifier: NCT00716755.

Intermittent cocaine administration produces sensitization, whereas the continuous administration of cocaine produces tolerance to the effects of subsequent cocaine administration during withdrawal. The present study examined whether the effects of these two dosing regimens are related to alterations in the functional status of dopamine (DA) D2 receptors. In all experiments, rats were withdrawn for 7 days from a 14-day pretreatment regimen involving either continuous or intermittent cocaine administration. Experiments examined changes in the behavioral response to an autoreceptor-selective dose of apomorphine, the effects of sulpiride on electrically stimulated DA release in striatal brain slices and striatal D2 receptor binding, and mRNA levels. The results indicate that the continuous administration of cocaine produces findings consistent with D2 autoreceptor supersensitivity; there was enhanced inhibition of behavior after the autoreceptor-selective dose of apomorphine, decreased electrically stimulated DA release in the absence of sulpiride, and enhanced electrically stimulated DA release in the presence of sulpiride. However, there were no changes in postsynaptic D2 receptor binding or mRNA levels. Intermittent cocaine administration did not produce evidence of D2 autoreceptor subsensitivity: there was no decrease in inhibition of behavior after the autoreceptor-selective dose of apomorphine, no changes in electrically stimulated DA release in the absence or presence of D2 receptor blockade, and no change in the levels of D2 receptor binding; however, D2 mRNA levels were decreased by 22%. Overall, the present results are consistent with the hypothesis that the expression of tolerance induced by continuous cocaine administration is associated with D2 autoreceptor supersensitivity.

International audience; The aim of this paper is to describe a 3D-2D ultrasound feature-based registration method for navigated prostate biopsy and its first results obtained on patient data. A system combining a low-cost tracking system and a 3D-2D registration algorithm was designed. The proposed 3D-2D registration method combines geometric and image-based distances. After extracting features from ultrasound images, 3D and 2D features within a defined distance are matched using an intensity...

The aim of this paper is to describe a 3D-2D ultrasound feature-based registration method for navigated prostate biopsy and its first results obtained on patient data. A system combining a low-cost tracking system and a 3D-2D registration algorithm was designed. The proposed 3D-2D registration method combines geometric and image-based distances. After extracting features from ultrasound images, 3D and 2D features within a defined distance are matched using an intensity-based function. The results are encouraging and show acceptable errors with simulated transforms applied on ultrasound volumes from real patients.

The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions. PMID:26044572

Dynamic alignment of D2 induced by two few-cycle pulses was investigated by solving the time-dependent Schr(o)dinger equation numerically based on a rigid rotor model. The results show that alignment of D2 can be enhanced by two few-cycle pulses compared with the level achievable by a single fewcycle pulse as long as the time delay between two pulses is chosen properly, and the pulse duration of two lasers plays an important role in the aligning process of D2 molecules.

Full Text Available Abstract Dopamine is an important catecholamine neurotransmitter modulating many physiological functions, and is linked to psychopathology of many diseases such as schizophrenia and drug addiction. Dopamine D1 and D2 receptors are the most abundant dopaminergic receptors in the striatum, and although a clear segregation between the pathways expressing these two receptors has been reported in certain subregions, the presence of D1-D2 receptor heteromers within a unique subset of neurons, forming a novel signaling transducing functional entity has been shown. Recently, significant progress has been made in elucidating the signaling pathways activated by the D1-D2 receptor heteromer and their potential physiological relevance.

Studies of in vivo dopamine receptors in schizophrenia have mostly focused on D2 receptors in striatal areas or on D1 receptors in cortex. No previous study has examined the correlation between cortical dopamine D2/3 receptor binding potentials and cognition in schizophrenia patients. The objective...... was to examine this relation in the frontal cortex in first-episode, drug-naive schizophrenia patients. Based on preclinical and pharmacological evidence, we specifically expected to find a relation between D2/3 receptor binding potentials and set shifting. This was a cross-sectional, case-control study using...... single-photon emission computerized tomography with the D2/3-receptor ligand [123I]epidepride, co-registered with structural magnetic resonance imaging and correlated to cognitive measures. Participants were 24 antipsychotic-naive, first-episode schizophrenia patients and 20 healthy controls matched...

Full Text Available Dopamine is a monoamine neurotransmitter of both central and peripheral nervous system. Its role in the neural-immune communication has been discussed in the present study. Results reveal that in vivo blockade of D2 dopamine receptor by means of sulpiride, a selective antagonist for D2 dopamine receptor produce changes in functional activities of the immune effector cells. Adults rats pretreated once with LPS (a bacterial product (25µg/250µl, i.p., produce an immune response, were subjected to i.p. injection with sulpiride (4 mg/kg b.w., i.p., a selective antagonist for D2 dopamine receptors, after 3 days postimmunization. After 18 days later, we assessed the total leukocyte number, neutrophils, eosinophils and basophils number. In summary, we provide that D2 dopamine receptor blockade suppress or enhance the immune effector cells number in restraint stress.

We present new observations of the D2CO emission towards the small cloud L1689N in the rho Ophiuchus complex. We surveyed five positions, three being a cut across a shock site and two probing the quiescent gas of the molecular cloud. We detected D2CO emission in the first three positions. The measured [D2CO]/[H2CO] is about 3%, whereas it is removed from the cold storage by the shock at the interface between the outflowing and quiescent gas. We review the predictions of the published models proposed to explain the observed high deuteration of formaldehyde. They fall in two basic schemes: gas phase and grain surface chemistry. None of the reviewed models is able to account for the observed [D2CO]/[H2CO] abundance ratio. A common characteristics shared by the models is apparently that all underestimate the atomic [D]/[H] ratio in the accreting gas.

The dynamics of molecular rotational wave packets of D2 induced by ultrashort laser pulses was investigated numerically by solving the time-dependent Schrodinger equation. Results show that an ultrashort pulse can manipulate a coherent rotational wave packet of D2 se-lectively. In the calculation, a first laser pulse was used to create a coherent rotational wave packet from an initial thermal ensemble of D2 at the temperature of 300 K. The second laser pulse was used to manipulate the rotational wave packet selectively around the first quarter and the three quarters revival. The alignment parameter and its Fourier transform amplitude both illustrate that the relative populations of even and odd rotational states in the final rotational wave packet of D2 can be manipulated by precisely selecting the time delay between the first and the second ultrashort pulse.

Introduction: In vitro, the dopamine D2 receptor exists in two states, with high and low affinity for agonists. The high-affinity state is the physiologically active state thought to be involved in dopaminergic illnesses such as schizophrenia. The positron emission tomography radiotracer [{sup 11}C](+)-PHNO ([{sup 11}C](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4] oxazin-9-o l), being a D2 agonist, should selectively label the high-affinity state at tracer dose and therefore be more susceptible to competition by agonist as compared to the antagonist [{sup 3}H]raclopride, which binds to both affinity states. Methods: We tested this prediction using ex vivo dual-radiotracer experiments in conscious rats. D2 antagonists (haloperidol or clozapine), a partial agonist (aripiprazole), a full agonist [(-)-NPA] or the dopamine-releasing drug amphetamine (AMPH) were administered to rats prior to an intravenous coinjection of [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride. Rats were sacrificed 60 min after radiotracer injection. Striatum, cerebellum and plasma samples were counted for {sup 11}C and {sup 3}H. The specific binding ratio {l_brace}SBR, i.e., [%ID/g (striatum)-%ID/g (cerebellum)]/(%ID/g (cerebellum){r_brace} was used as the outcome measure. Results: In response to D2 antagonists, partial agonist or full agonist, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs responded indistinguishably in terms of both ED{sub 50} and Hill slope (e.g., (-)-NPA ED{sub 50} values are 0.027 and 0.023 mg/kg for [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride, respectively). In response to AMPH challenge, [{sup 11}C](+)-PHNO and [{sup 3}H]raclopride SBRs were inhibited to the same degree. Conclusions: We have shown that the SBRs of [{sup 11}C](+)-PHNO- and [{sup 3}H]raclopride do not differ in their response to agonist challenge. These results do not support predictions of the in vivo binding behavior of a D2 agonist radiotracer and cast some doubt on the in vivo

Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.

Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized that blockade of D2 receptors might facilitate extinction in mice, while agonists should block extinction, as they do in rats. One day after fear con...

Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially ...

AIM: To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer. METHODS: Clinicopathological data from 209 patients with gastric cancer, who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011, were analyzed retrospectively. Among these patients, 131 patients underwent laparoscopy-assisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG). The parameters analyzed included operative time, blood loss, blood transfusion, morbidity, mortality, the number of harvested lymph nodes (HLNs), and pathological stage. RESULTS: There were no significant differences in sex, age, types of radical resection [radical proximal gastrectomy (PG + D2), radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)], and stages between the LAG and OG groups (P > 0.05). Among the two groups, 127 cases (96.9%) and 76 cases (97.4%) had 15 or more HLNs, respectively. The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P = 0.233). In the same type of radical resection, there were no significant differences in the number of HLNs between the two groups (PG + D2: 21.7 ± 7.5 vs 22.4 ± 9.3; DG + D2: 25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2: 30.9 ± 13.4 vs 29.3 ± 10.4; P > 0.05 for all comparisons). Tumor free margins were obtained in all cases. Compared with OG group, the LAG group had significantly less blood loss, but a longer operation time (P dissection is equivalent to OG in the number of HLNs, regardless of tumor location. Thus, this procedure can achieve the same radicalness as OG. PMID:22371644

Full-duplex (FD) communication is optimistically promoted to double the spectral efficiency if sufficient self-interference cancellation (SIC) is achieved. However, this is not true when deploying FD-communication in a large-scale setup due to the induced mutual interference. Therefore, a large-scale study is necessary to draw legitimate conclusions about gains associated with FD-communication. This paper studies the FD operation for underlay device-to-device (D2D) communication sharing the uplink resources in cellular networks. We propose a disjoint fine-tuned selection criterion for the D2D and FD modes of operation. Then, we develop a tractable analytical paradigm, based on stochastic geometry, to calculate the outage probability and rate for cellular and D2D users. The results reveal that even in the case of perfect SIC, due to the increased interference injected to the network by FD-D2D communication, having all proximity UEs transmit in FD-D2D is not beneficial for the network. However, if the system parameters are carefully tuned, non-trivial network spectral-efficiency gains (64% shown) can be harvested. We also investigate the effects of imperfect SIC and D2D-link distance distribution on the harvested FD gains.

Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.

Some previous studies have suggested that patients with social anxiety disorder (SAD) have a hypoactive central dopaminergic system. Supporting this there have been reports from neuroimaging studies of reduced striatal D2 receptor binding in subjects with SAD. The aim of this study was to investigate D2 receptor sensitivity in patients with SAD compared with a group of matched, healthy controls using a neuroendocrine challenge with the selective D2 antagonist, sulpiride. D2 receptor function was assessed in 23 subjects with generalized SAD and 23 matched, healthy controls using a challenge with 400 mg of a selective D2 antagonist, sulpiride in a randomized, placebo-controlled, crossover design. Response to sulpiride was measured by the change in prolactin level and changes in self-rated measures of social anxiety, mood and the ability to experience pleasure. There was no significant difference in prolactin response to sulpiride between the two groups. Sulpiride resulted in no effect in either the SAD or healthy control group on measures of social anxiety, mood or the ability to experience pleasure. Contrary to our hypothesis, in this study we found no evidence of reduced D2 receptor function in subjects with SAD compared with healthy controls.

Summary Striatal dopamine transmission underlies numerous goal-directed behaviors. Medium spiny neurons (MSNs) are a major target of dopamine in the striatum. However, as dopamine does not directly evoke a synaptic event in MSNs, the time course of dopamine signaling in these cells remains unclear. To examine how dopamine release activates D2-receptors on MSNs, G-protein activated inwardly rectifying potassium (GIRK2; Kir 3.2) channels were virally overexpressed in the striatum and the resulting outward currents were used as a sensor of D2-receptor activation. Electrical and optogenetic stimulation of dopamine terminals evoked robust D2-receptor inhibitory post-synaptic currents (IPSCs) in GIRK2-expressing MSNs that occurred in under a second. Evoked D2-IPSCs could be driven by repetitive stimulation and were not occluded by background dopamine tone. Together, the results indicate that D2-receptors on MSNs exhibit functional low affinity and suggest that striatal D2-receptors can encode both tonic and phasic dopamine signals. PMID:25242218

We present state-to-state differential cross sections for collisions of NO molecules (X2Π1 /2 ,j =1 /2 ,f ) with He atoms and ortho-D2 (j = 0) molecules as a function of collision energy. A high angular resolution obtained using the combination of Stark deceleration and velocity map imaging allows for the observation of diffraction oscillations in the angular scattering distributions. Differences in the differential cross sections and, in particular, differences in the angular spacing between individual diffraction peaks are observed. Since the masses of D2 and He are almost equal and since D2(j = 0) may be considered as a pseudo-atom, these differences directly reflect the larger size of D2 as compared to He. The observations are in excellent agreement with the cross sections obtained from quantum close-coupling scattering calculations based on accurate ab initio NO-He and NO-D2 potential energy surfaces. For the latter, we calculated a new NO-D2 potential energy surface.

To identify if there is a relationship between the deiodinase D2-Thr92Ala genetic variant, thyroid hormone levels and biochemical hypothyroidism in preeclampsia. We genotyped 125 women with preeclampsia and 131 normal pregnant women using PCR-RFLP. Serum thyroid hormone levels were determined using ELISA. Our study showed higher TSH and FT4 levels and lower FT3 levels in women with preeclampsia compared to normal pregnant women, with statistical significance for women with mild and severe preeclampsia. The risk to develop pregnancy-induced hypertension (PIH), mild or severe preeclampsia was increased in carriers of at least one D2-Ala92 allele. TSH and FT4 levels were significantly higher and FT3 levels were significantly lower in preeclamptic women with severe preeclampsia if they carried the D2-Ala92 allele compared to non-carriers. Pregnant women with PIH and mild preeclampsia, carriers of at least one D2-Ala92 allele, delivered at lower gestational age neonates with a lower birth weight compared to non-carriers, but the results were statistically significant only in severe preeclampsia. The D2-Thr92Ala genetic variant is associated with the severity and the obstetric outcome of preeclampsia, and it also influences thyroid hormone levels. The study demonstrates non-thyroidal biochemical hypothyroidism - as a result of deiodination effects due to D2 genotypes.

Drug addiction and obesity share the core feature that those afflicted by the disorders express a desire to limit drug or food consumption yet persist despite negative consequences. Emerging evidence suggests that the compulsivity that defines these disorders may arise, to some degree at least, from common underlying neurobiological mechanisms. In particular, both disorders are associated with diminished striatal dopamine D2 receptor (D2R) availability, likely reflecting their decreased maturation and surface expression. In striatum, D2Rs are expressed by approximately half of the principal medium spiny projection neurons (MSNs), the striatopallidal neurons of the so-called 'indirect' pathway. D2Rs are also expressed presynaptically on dopamine terminals and on cholinergic interneurons. This heterogeneity of D2R expression has hindered attempts, largely using traditional pharmacological approaches, to understand their contribution to compulsive drug or food intake. The emergence of genetic technologies to target discrete populations of neurons, coupled to optogenetic and chemicogenetic tools to manipulate their activity, have provided a means to dissect striatopallidal and cholinergic contributions to compulsivity. Here, we review recent evidence supporting an important role for striatal D2R signaling in compulsive drug use and food intake. We pay particular attention to striatopallidal projection neurons and their role in compulsive responding for food and drugs. Finally, we identify opportunities for future obesity research using known mechanisms of addiction as a heuristic, and leveraging new tools to manipulate activity of specific populations of striatal neurons to understand their contributions to addiction and obesity.

We report the results of high field magnetization measurements on a powder sample of NiCu (pba)(D2O)32D2O (pba = 1,3-propylenebis(oxamato), C7H6N2O6) which is regarded as a ferrimagnetic chain composed of spins S = 1/2 and 1. From a fit of the susceptibility of this compound to numerical calculations (exact diagonalization for ten sites), we evaluated the exchange constant J/kB = 121 K. In the magnetization measurements at 10 K up to 50 T, we observed a magnetization plateau of about 1.1 μB/(formula unit) corresponding to about one-third of the saturated magnetization. The increase of the magnetization at low magnetic fields is discussed and compared with some calculations.

为了提高步态识别率,在步态能量图(gait energy image,GEI)基础上,提出了基于小波包分解(waveletpacket decomposition,WPD)和完全主成分分析(two-directional two-dimensional principal component analysis,(2D)2PCA)的步态识别方法.该方法采用基于人体轮廓的GEI来解决步态数据量过大的问题,并采用WPD和(2D)2PCA进行步态特征提取,解决了已有基于小波变换的步态识别方法中高频分量丢失或维数过高问题.在NLPR步态数据库上对该方法进行了评测,并与经典方法进行了比较.实验结果表明:该方法具有更高的识别率和视角变化的鲁棒性.%To improve the gait recognition rate,a gait recognition method based on wavelet packet decomposition (WPD) and two-directional two-dimensional principal component analysis ((2D)2PCA)was proposed.In the method,gait energy image (GEI) of the body silhouette was firstly adopted to solve the problem of huge gait data.And then,WPD and (2D)2PCA were used to extract features to solve the problem existing in the gait recognition method based on wavelet transform at present:high frequency component loss or high dimension problem.The Experiment evaluation was conducted on NLPR gait database and compared with classical methods.Result shows that the proposed method has a higher recognition rate and is more robust to the change of view.

Full Text Available "nBackground: Dopaminergic is the most important neurotransmitter is fear. The dopaminergic mesolimbic pathway has essential role in excitable behavior, and it's role in Parkinson disease. The aim of this research in study, the effect of dopaminergic pathway in fear response. "n"nMethods: The elevated plus maze was used in combination with the percentage of time spent in the open arms of the maze (OAT% and the percentage of entries into the open arms (OAE% to measure fear. Increases in the OAT% and OAE% indicate an anxiolytic effect (reduction in anxiety, whereas decreases in the OAE% and OAT% indicate an anxiogenic effect. After five days, the rats were injected with saline and different doses of sulpiride and Bromocriptine."n"nResults: Results showed that intracerebroventricular administration of sulpiride, in the doses of 5, 20μg/rat and bromocriptine, D2 agonist in doses 65, 95μg/rat produced a significant effect comparing to sham groups (p<0.05. While intracerebroventricular administration of sulpiride 15, 10μg/rat, and bromocriptine 70, 80μg/rat, did not show any significant effect comparing with sham group (p<0.05. In the current research intracerebroventricular administration of sulpiride, D2 antagonist at the doses of 5, 10, 15, 20μg/rat and Bromocriptine, D2 agonist in the doses of 65, 70, 80, 95μg/rat were used and theire effect on the fear behavior were studied. "n"nConclusions: The possible effect of Dopaminergic system in the fear process, especially D2 receptor increase fear.

Brief dopamine events are critical actors of reward-mediated learning in the striatum; the intracellular cAMP-protein kinase A (PKA) response of striatal medium spiny neurons to such events was studied dynamically using a combination of biosensor imaging in mouse brain slices and in silico simulations. Both D1 and D2 medium spiny neurons can sense brief dopamine transients in the sub-micromolar range. While dopamine transients profoundly change cAMP levels in both types of medium spiny neurons, the PKA-dependent phosphorylation level remains unaffected in D2 neurons. At the level of PKA-dependent phosphorylation, D2 unresponsiveness depends on protein phosphatase-1 (PP1) inhibition by DARPP-32. Simulations suggest that D2 medium spiny neurons could detect transient dips in dopamine level. The phasic release of dopamine in the striatum determines various aspects of reward and action selection, but the dynamics of the dopamine effect on intracellular signalling remains poorly understood. We used genetically encoded FRET biosensors in striatal brain slices to quantify the effect of transient dopamine on cAMP or PKA-dependent phosphorylation levels, and computational modelling to further explore the dynamics of this signalling pathway. Medium-sized spiny neurons (MSNs), which express either D1 or D2 dopamine receptors, responded to dopamine by an increase or a decrease in cAMP, respectively. Transient dopamine showed similar sub-micromolar efficacies on cAMP in both D1 and D2 MSNs, thus challenging the commonly accepted notion that dopamine efficacy is much higher on D2 than on D1 receptors. However, in D2 MSNs, the large decrease in cAMP level triggered by transient dopamine did not translate to a decrease in PKA-dependent phosphorylation level, owing to the efficient inhibition of protein phosphatase 1 by DARPP-32. Simulations further suggested that D2 MSNs can also operate in a 'tone-sensing' mode, allowing them to detect transient dips in basal dopamine. Overall

Objective To establish a RP-HPLC method for the content determination of vitamin D2 in Vitamin D2 and Calcium Hydrogen Phosphate Tablets.Methods The chromatographic column of AlltimaTM C18 was adopted with the mobile phase of acetonitrilemethanol(1∶9).The detection wavelength was set at 265 nm,the flow velocity was 1.0 mL/min and column temperature was 30 ℃.Results The sample size of vitamin D2 within the range of 0.005-0.065 μg(r=1.000 0)showed the good linearity with the peak area.The mean recovery rate was 99.38％,RSD =0.68％ (n =9).Conclusion This method has the advantages of rapidness,simpleness,accuracy and low test cost,and can be used for the quality control of vitamin D2 in Vitamin D2 and Calcium Hydrogen Phosphate Tablets.%目的 建立测定维D2磷酸氢钙片中维生素D2含量的反相高效液相色谱法.方法 采用Alhima C18色谱柱(250 mm×4.6mm,5 μm),流动相为乙腈-甲醇(1∶9),检测波长为265 nm,流速为1.0 mL/min,柱温30℃.结果 维生素D2进样量在0.005～0.065 μg范围内与峰面积具有良好的线性关系,r=1.0000,平均回收率为99.38％,RSD＝0.68％(n＝9).结论 该法具有快速、简便、准确、检验成本低的优点,可用于维D2磷酸氢钙片中维生素D2的质量控制.

Full Text Available Abstract Background Neurotensin (NT is known to act on dopamine (DA neurons at the somatodendritic level to regulate cell firing and secondarily enhance DA release. In addition, anatomical and indirect physiological data suggest the presence of NT receptors at the terminal level. However, a clear demonstration of the mechanism of action of NT on dopaminergic axon terminals is lacking. We hypothesize that NT acts to increase DA release by inhibiting the function of terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic voltammetry (FCV to monitor in real time the axonal release of DA in the nucleus accumbens (NAcc. Results DA release was evoked by single electrical pulses and pulse trains (10 Hz, 30 pulses. Under these two stimulation conditions, we evaluated the characteristics of DA D2 autoreceptors and the presynaptic action of NT in the NAcc shell and shell/core border region. The selective agonist of D2 autoreceptors, quinpirole (1 μM, inhibited DA overflow evoked by both single and train pulses. In sharp contrast, the selective D2 receptor antagonist, sulpiride (5 μM, strongly enhanced DA release triggered by pulse trains, without any effect on DA release elicited by single pulses, thus confirming previous observations. We then determined the effect of NT (8–13 (100 nM and found that although it failed to increase DA release evoked by single pulses, it strongly enhanced DA release evoked by pulse trains that lead to prolonged DA release and engage D2 autoreceptors. In addition, initial blockade of D2 autoreceptors by sulpiride considerably inhibited further facilitation of DA release generated by NT (8–13. Conclusion Taken together, these data suggest that NT enhances DA release principally by inhibiting the function of terminal D2 autoreceptors and not by more direct mechanisms such as facilitation of terminal calcium influx.

The neuromodulator dopamine plays an important role in synaptic plasticity. The effects depend on receptor subtypes, affinity, concentration level, and the kind of neuroplasticity induced. In animal experiments, dopamine D2-like receptor stimulation revealed partially antagonistic effects on plasticity, which might be explained by dosage dependency. In humans, D2 receptor block abolishes plasticity, and the D2/D3, but predominantly D3, receptor agonist ropinirol has a dosage-dependent nonlinear affect on plasticity. Here we aimed to determine the specific affect of D2 receptor activation on neuroplasticity in humans, because physiological effects of D2 and D3 receptors might differ. Therefore, we combined application of the selective D2 receptor agonist bromocriptine (2.5, 10, and 20 mg or placebo medication) with anodal and cathodal transcranial direct current stimulation (tDCS), which induces nonfocal plasticity, and with paired associative stimulation (PAS) generating a more focal kind of plasticity in the motor cortex of healthy humans. Plasticity was monitored by transcranial magnetic stimulation-induced motor-evoked potential amplitudes. For facilitatory tDCS, bromocriptine prevented plasticity induction independent from drug dosage. However, its application resulted in an inverted U-shaped dose-response curve on inhibitory tDCS, excitability-diminishing PAS, and to a minor degree on excitability-enhancing PAS. These data support the assumption that modulation of D2-like receptor activity exerts a nonlinear dose-dependent effect on neuroplasticity in the human motor cortex that differs from predominantly D3 receptor activation and that the kind of plasticity-induction procedure is relevant for its specific impact.

Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism.

Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

Cs2FeCl5.D2O has been identified as a linear magnetoelectric material, although the correlation of this property with the magnetic structures of this compound has not been adequately studied. We have used single-crystal and powder neutron diffraction to obtain detailed information about its nuclear and magnetic structures. From the nuclear structure analysis, we describe the occurrence of a phase transition related to the reorganization of the [FeCl5.D2O] -2 ions and the Cs+ counterion. The magnetic structure was determined at zero magnetic field at 1.8 K using single-crystal diffraction and its temperature evolution was recorded using powder diffraction. The symmetry analysis of the magnetic structure is compatible with the occurrence of the magnetoelectric effect. Moreover, the evolution of the magnetic structure as a function of the external magnetic field has also been studied. The reorientation of the magnetic moments under applied external field along the easy axis (b axis at low temperature) is compatible with the occurrence of a spin-flop transition. The application of a magnetic field below TN compels the magnetic moments to flip from the b axis to the a c plane (with a small induced component along the b axis), for a critical magnetic field of ca. 1.2 T.

The serotonin 5-HT1A receptor (5-HT1 A R) and dopamine D2 receptor (D2 R) have been implicated as important sites of action in antipsychotics. Several lines of evidence indicate the key role of G protein-coupled receptors (GPCRs) heteromers in pathophysiology of schizophrenia and highlight these complexes as novel drug targets. Because heterodimers can form only on those cells co-expressing constituent receptors, they present a target of high pharmacological specificity in the context of biochemical effects induced by antipsychotic drugs. In studies conducted in the HEK 293 cell line, we demonstrated that 5-HT1 A R and D2 R are able to form constitutive heterodimers, and antipsychotic drugs (clozapine, olanzapine, aripiprazole, and lurasidone) enhanced this process, with clozapine being most effective. Various functional tests (cAMP and IP1 as well as ERK activation) indicated that the drugs had different effects on signal transduction by the heteromer. Interestingly, co-incubation of heterodimer-expressing HEK 293 cells with clozapine and the 5-HT1 A R agonist 8-OH DPAT potentiated post-synaptic effects, especially with respect to ERK activation. Our results indicate that the D2 -5-HT1A complex possesses biochemical, pharmacological, and functional properties distinct from those of mono- and homomers. This result has implications for the development of improved pharmacotherapy for schizophrenia or other disorders (activating the heteromer might be cognitive enhancing, since it is expressed in frontal cortex) through the specific targeting of heterodimers. We reported the constitutive formation of D2 -5-HT1A heteromers, which possess biochemical, pharmacological, and functional properties distinct from those of mono- and homomers, as revealed by antipsychotics action. We also showed that these two receptors are co-expressed in mouse cortical neurons; therefore their potential to heterodimerize may comprise an essential target for the development of novel strategies

The striatum can be divided into the DLS (dorsolateral striatum) and the VMS (ventromedial striatum), which includes NAcC (nucleus accumbens core) and NAcS (nucleus accumbens shell). Here, we examined differences in electrophysiological properties of MSSNs (medium-sized spiny neurons) based on their location, expression of DA (dopamine) D1/D2 receptors and responses to the μ-opioid receptor agonist, DAMGO {[D-Ala(2)-MePhe(4)-Gly(ol)(5)]enkephalin}. The main differences in morphological and biophysical membrane properties occurred among striatal sub-regions. MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances) compared with cells in the VMS. RMPs (resting membrane potentials) were similar among regions except for D2 cells in the NAcC, which displayed a significantly more depolarized RMP. In contrast, differences in frequency of spontaneous excitatory synaptic inputs were more prominent between cell types, with D2 cells receiving significantly more excitatory inputs than D1 cells, particularly in the VMS. Inhibitory inputs were not different between D1 and D2 cells. However, MSSNs in the VMS received more inhibitory inputs than those in the DLS. Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount. DAMGO also increased cellular excitability in the VMS, as shown by reduced threshold for evoking APs (action potentials). Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

Full Text Available The striatum can be divided into the DLS (dorsolateral striatum and the VMS (ventromedial striatum, which includes NAcC (nucleus accumbens core and NAcS (nucleus accumbens shell. Here, we examined differences in electrophysiological properties of MSSNs (medium-sized spiny neurons based on their location, expression of DA (dopamine D1/D2 receptors and responses to the μ-opioid receptor agonist, DAMGO {[D-Ala2-MePhe4-Gly(ol5]enkephalin}. The main differences in morphological and biophysical membrane properties occurred among striatal sub-regions. MSSNs in the DLS were larger, had higher membrane capacitances and lower Rin (input resistances compared with cells in the VMS. RMPs (resting membrane potentials were similar among regions except for D2 cells in the NAcC, which displayed a significantly more depolarized RMP. In contrast, differences in frequency of spontaneous excitatory synaptic inputs were more prominent between cell types, with D2 cells receiving significantly more excitatory inputs than D1 cells, particularly in the VMS. Inhibitory inputs were not different between D1 and D2 cells. However, MSSNs in the VMS received more inhibitory inputs than those in the DLS. Acute application of DAMGO reduced the frequency of spontaneous excitatory and inhibitory postsynaptic currents, but the effect was greater in the VMS, in particular in the NAcS, where excitatory currents from D2 cells and inhibitory currents from D1 cells were inhibited by the largest amount. DAMGO also increased cellular excitability in the VMS, as shown by reduced threshold for evoking APs (action potentials. Together the present findings help elucidate the regional and cell-type-specific substrate of opioid actions in the striatum and point to the VMS as a critical mediator of DAMGO effects.

A number of signaling pathways underlying pathological cardiac hypertrophy have been identified. However, few studies have probed the functional significance of these signaling pathways in the context of exercise or physiological pathways. Exercise studies were performed on females from six different genetic mouse models that have been shown to exhibit alterations in pathological cardiac adaptation and hypertrophy. These include mice expressing constitutively active glycogen synthase kinase-3β (GSK-3βS9A), an inhibitor of CaMK II (AC3-I), both GSK-3βS9A and AC3-I (GSK-3βS9A/AC3-I), constitutively active Akt (myrAkt), mice deficient in MAPK/ERK kinase kinase-1 (MEKK1(-/-)), and mice deficient in cyclin D2 (cyclin D2(-/-)). Voluntary wheel running performance was similar to NTG littermates for five of the mouse lines. Exercise induced significant cardiac growth in all mouse models except the cyclin D2(-/-) mice. Cardiac function was not impacted in the cyclin D2(-/-) mice and studies using a phospho-antibody array identified six proteins with increased phosphorylation (greater than 150%) and nine proteins with decreased phosphorylation (greater than 33% decrease) in the hearts of exercised cyclin D2(-/-) mice compared to exercised NTG littermate controls. Our results demonstrate that unlike the other hypertrophic signaling molecules tested here, cyclin D2 is an important regulator of both pathologic and physiological hypertrophy. Impact statement This research is relevant as the hypertrophic signaling pathways tested here have only been characterized for their role in pathological hypertrophy, and not in the context of exercise or physiological hypertrophy. By using the same transgenic mouse lines utilized in previous studies, our findings provide a novel and important understanding for the role of these signaling pathways in physiological hypertrophy. We found that alterations in the signaling pathways tested here had no impact on exercise performance. Exercise

AIM:To evaluate the radicalness and safety of laparoscopic D2 dissection for gastric cancer.METHODS:Clinicopathological data from 209 patients with gastric cancer,who underwent radical gastrectomy with D2 dissection between January 2007 and February 2011,were analyzed retrospectively.Among these patients,131 patients underwent laparoscopyassisted gastrectomy (LAG) and 78 underwent open gastrectomy (OG).The parameters analyzed included operative time,blood loss,blood transfusion,morbidity,mortality,the number of harvested lymph nodes (HLNs),and pathological stage.RESULTS:There were no significant differences in sex,age,types of radical resection [radical proximal gastrectomy (PG + D2),radical distal gastrectomy (DG + D2) and radical total gastrectomy (TG + D2)],and stages between the LAG and OG groups (P ＞ 0.05).Among the two groups,127 cases (96.9％) and 76 cases (97.4％) had 15 or more HLNs,respectively.The average number of HLNs was 26.1 ± 11.4 in the LAG group and 24.2 ± 9.3 in the OG group (P =0.233).In the same type of radical resection,there were no significant differences in the number of HLNs between the two groups (PG + D2:21.7 ± 7.5 vs 22.4 4-9.3;DG + D2:25.7 ± 11.0 vs 22.3 ± 7.9; TG + D2:30.9 ± 13.4 vs 29.3 ± 10.4; P ＞ 0.05 for all comparisons).Tumor free margins were obtained in all cases.Compared with OG group,the LAG group had significantly less blood loss,but a longer operation time (P ＜ 0.001).The morbidity of the LAG group was 9.9％,which was not significantly different from the OG group (7.7％) (P=0.587).The mortality was zero in both groups.CONCLUSION:Laparoscopic D2 dissection is equivalent to OG in the number of HLNs,regardless of tumor location.Thus,this procedure can achieve the same radicalness as OG.

The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour...... of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered...... a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P vitamin D2 per 100 g of fresh mushrooms and comparable to levels found...

Full Text Available BACKGROUND: A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system clearly reduces conditioned fear. Injections of haloperidol, a preferential D2 receptor antagonist, into the inferior colliculus (IC enhance the processing of unconditioned aversive information. However, a clear characterization of the interplay of D2 receptors in the mediation of unconditioned and conditioned fear is still lacking. METHODS: The present study investigated the effects of intra-IC injections of the D2 receptor-selective antagonist sulpiride on behavior in the elevated plus maze (EPM, auditory-evoked potentials (AEPs to loud sounds recorded from the IC, fear-potentiated startle (FPS, and conditioned freezing. RESULTS: Intra-IC injections of sulpiride caused clear proaversive effects in the EPM and enhanced AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not affect FPS or conditioned freezing. CONCLUSIONS: Dopamine D2-like receptors of the inferior colliculus play a role in the modulation of unconditioned aversive information but not in the fear-potentiated startle response.

Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals. PMID:28233850

Retinal light responsiveness measured via electroretinography undergoes developmental modulation and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study is to determine whether the dopamine D2 receptor regulates the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild type mice and mice with a genetic deletion of the gene that encodes the dopamine D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that mutation of the dopamine D2 receptors preferentially increases the amplitude of the inner retinal light responses evoked by high intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, the a-wave, b-wave and oscillatory potentials, increase with age. Comparatively, mutation of the dopamine D2 receptors preferentially reduces the age-dependent increase of b-waves evoked by low intensity light. Light deprivation from birth reduces the amplitude of b-waves and completely diminishes the increased amplitude of oscillatory potentials. Taken together, these results demonstrate that the dopamine D2 receptor plays an important role in the activity-dependent functional development of the mouse retina. PMID:25393815

We compare time of flight spectra of atomic D + and molecular D2+ ions specularly scattered from a polycrystalline nickel surface at 4° of incidence and with a velocity corresponding to 1 keV/u. Molecular dissociation is assumed to occur mostly upon resonant neutralisation into the antibonding triplet state of D2. The kinetic energy released in the dissociation (KER) is distributed over both atomic fragments. We consider the D2+ spectrum as the result of atomic projectiles hitting the surface at different energies and different incidence or azimuthal angles given by the cinematic of the fragmentation. The electronic density of states of Ni, the vibrational levels of D2+ and the image potential shift are taken into consideration to calculate the KER distribution. The resulting broadening function is then applied to the experimental D + spectrum, which is finally compared to the spectrum of D2+. The good agreement found without any adjustable parameter is consistent with the assumption of a complete dissociation by resonant neutralisation on the incoming path.

Although in most cases one can easily distinguish between atypical fibroxanthomas and angiosarcomas, hemorrhagic atypical fibroxanthomas can pose a diagnostic problem. In rare cases, the large atypical cells of atypical fibroxanthoma can stain with CD31, leading to the erroneous diagnosis of angiosarcoma. We elected to further study this conundrum with 2 additional markers of lymphatic and vascular elements, namely D2-40 (podoplanin) and Fli-1, respectively. We studied 26 cases of atypical fibroxanthoma and 20 cases of angiosarcoma with Fli-1 and D2-40. We found that both Fli-1 and D2-40 stained a majority of cases of angiosarcoma (16/20 and 12/20, respectively), although only staining a minority of cases of atypical fibroxanthoma (8/26 for both). In addition, D2-40 staining of atypical fibroxanthoma was usually weak when positive, whereas Fli-1 staining of angiosarcomas was mostly strong and nuclear. Thus, both D2-40 and Fli-1 seem to be useful in distinguishing between atypical fibroxanthomas and angiosarcomas.

The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.

Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same.

Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals.

Two hundred and fifty-one 12C2D2 transitions have been measured in the 0.2-1.6 THz region of its ν5-ν4 difference band and 202 of them were observed for the first time. The accuracy of these measurements is estimated to be ranging from 50 kHz to 100 kHz. The 12C2D2 molecules were generated under room temperature by passing 120-150 mTorr D2O vapor through calcium carbide (CaC2) powder. A multistate analysis was carried out for the bending vibrational modes ν4 and ν5 of 12C2D2, which includes the lines observed in this work and prior microwave, far-infrared and infrared data on the pure bending levels. Significantly improved molecular parameters were obtained for 12C2D2 by adding the new measurements to the old data set, which had only 10 lines with microwave measurement precision. New frequency and intensity predictions have been made based on the obtained molecular parameters. The more precise measurements and new predictions reported here will support the analyses of astronomical observations by the future high-resolution spectroscopy telescopes such as Herschel, SOFIA, and ALMA, which will work in the terahertz spectral region.

In this work, we systematically study the strong decay behavior of the charmed mesons D1*(2680 ), D3*(2760 ), and D2*(3000 ) reported by the LHCb Collaboration. By comparing the masses and the decay properties with the results of the experiment, we assign these newly observed mesons as the 2 S 1/2 1-, 1 D 5/2 3-, and 1 F 5/2 2+ states, respectively. As a byproduct, we also study the strong decays of the unobserved 2 P 3/2 2+, 2 F 5/2 2+, and 3 P 3/2 2+ charmed mesons, which is useful for future experiments in searching for these charmed mesons.

In this work, we systematically study the strong decay behaviors of the charmed mesons $D_{1}^{*}(2680)$, $D_{3}^{*}(2760)$ and $D_{2}^{*}(3000)$ reported by the LHCb collaboration. By comparing the masses and the decay properties with the results of the experiment, we assigned these newly observed mesons as the $2S\\frac{1}{2}1^{-}$, $1D\\frac{5}{2}3^{-}$ and $1F\\frac{5}{2}2^{+}$ states respectively. As a byproduct, we also study the strong decays of the unobserved $2P\\frac{3}{2}2^{+}$ and $2F\\frac{5}{2}2^{+}$ charmed mesons, which is helpful to the future experiments in searching for these charmed mesons.

({sup 125}I) Iodosulpride binding was examined on eight human cell lines derived from lung, breast and digestive tract carcinomas, neuroblastomas and leukemia. Specific binding was detected in five of these cell lines. In the richest cell line N417, derived from small cell lung carcinoma, ({sup 125}I) iodosulpride bound with a high affinity (Kd = 1.3 nM) to an apparently homogeneous population of binding site (Bmax = 1,606 sites per cell). These sites displayed a typical D-2 specificity, established with several dopaminergic agonists and antagonists selective of either D-1 or D-2 receptor subtypes. In addition, dopamine, apomorphine and RU 24926 distinguished high- and low-affinity sites, suggesting that the binding sites are associated with a G-protein. The biological significance and the possible diagnostic implication of the presence of D-2 receptors on these cell lines are discussed.

Metabolic syndrome is a major risk factor for the development of diabetes mellitus and cardiovascular diseases. Pharmacological antagonism of the mineralocorticoid receptor (MR), a ligand-activated transcription factor, limits metabolic syndrome in preclinical models, but mechanistic studies are lacking to delineate the role of MR activation in adipose tissue. In this study, we report that MR expression is increased in visceral adipose tissue in a preclinical mouse model of metabolic syndrome and in obese patients. In vivo conditional upregulation of MR in mouse adipocytes led to increased weight and fat mass, insulin resistance, and metabolic syndrome features without affecting blood pressure. We identified prostaglandin D2 synthase as a novel MR target gene in adipocytes and AT56, a specific inhibitor of prostaglandin D2 synthase enzymatic activity, blunted adipogenic aldosterone effects. Moreover, translational studies showed that expression of MR and prostaglandin D2 synthase is strongly correlated in adipose tissues from obese patients.

Using semi-empirical density functional theory and the quasi-classical trajectory (QCT) method, a specific reaction parameter (SRP) density functional is developed for the dissociation of dihydrogen on Pt(1 1 1). The validity of the QCT method was established by showing that QCT calculations on reaction of D2 with Pt(1 1 1) closely reproduce quantum dynamics results for reaction of D2 in its rovibrational ground state. With the SRP functional, QCT calculations reproduce experimental data on D2 sticking to Pt(1 1 1) at normal and off-normal incidence with chemical accuracy. The dissociation of dihydrogen on Pt(1 1 1) is non-activated, exhibiting a minimum barrier height of -8 meV.

A specific-wavelength infrared (IR) light (λ =3140 nm) was irradiated into a solid D2 ice prepared in a cylinder target cell.The temperature in the solid D2 ice oscillated periodicaily with a high amplitude when irradiated by the IR light.The temperature oscillation has been well explained based on the two-dimensional heat transfer theory plus the IR-irradiation effect.The transmission optical imaging reveals that such a temperature oscillation is favorable to recrystallize the solid D2 ice from multicrystal to quasi single crystal.This suggests an efficient method to layer the solid hydrogen-isotope ice for the inertial-confinement-fusion (ICF) experiments.

Device-to-device (D2D) communication is considered as one of the key technologies to support new types of services, such as public safety and proximity-based applications. D2D communication requires a discovery phase, i.e., the node awareness procedure prior to the communication phase. Conventional...... half duplex transmission may not be sufficient to provide fast discovery and cope with the strict latency targets of future 5G services. On the other hand, in-band full duplex, by allowing simultaneous transmission and reception, may complete the discovery phase faster. In this paper, the potential...... of full duplex in providing fast discovery for the next 5th generation (5G) system supporting D2D communication is investigated. A design for such system is presented and evaluated via simulations, showing that full duplex can accelerate the discovery phase by supporting a higher transmission probability...

We report term energies and effective quantum numbers of the odd parity 3d2D → nf 2F series of lithium using multi-step and multi-photon laser excitation schemes. The experiments were performed using three dye lasers simultaneously pumped by the second harmonic (532 nm) of a Q-switched Nd:YAG laser in conjunction with an atomic beam apparatus and thermionic diode ion detector. The first ionization potential of lithium has been determined as 43,487.13 ± 0.02 cm- 1 from the much extended 3d2D → nf 2F (17 ≤ n ≤ 70) series. In addition, the oscillator strengths of the 3d2D → nf 2F (15 ≤ n ≤ 48) transitions have been determined, showing a decreasing trend with the increase in principal quantum number n.

Femtosecond vacuum ultraviolet pulses from a monochromated high harmonic generation source excite vibrational wavepackets in the {B}1{{{Σ }}}{{g}}+ state of D2. The wavepacket motion is measured through strong field ionization into bound and dissociative ion states yielding {{{D}}}2+ and D+ products. The time dependence of the {{{D}}}2+ and D+ ion signals provides a sensitive fingerprint of the quantum nuclear wavepacket, due to the different ionization rates for the two channels. The experiments are modelled with excitation and ionization processes included explicitly, with the results of the model showing a very good agreement with the experimental observations. The experiment demonstrates the level of detail attainable when studying ultrafast quantum nuclear dynamics using high harmonic sources.

This study demonstrates the evaluation and comparison of the lubricity properties of the biolubricants prepared from the feed stocks such as canola oil and canola biodiesel. Biolubricant from canola biodiesel has a lowcloud and pour point properties, better friction and antiwear properties, low phase transition temperature, is less viscous, and has the potential to substitute petroleum-based automotive lubricants. Biolubricant from canola oil has high thermal stability and is more viscous and more effective at higher temperature conditions. This study elucidates that both the biolubricants are attractive, renewable, and ecofriendly substitutes for the petroleum-based lubricants.

Since carbon-based structures of various dimensions, including one-dimensional (1D) carbon nanotubes, two-dimensional (2D) graphene and three-dimensional (3D) carbon foams, have attracted significant attention as microwave absorption fillers, we present an exceptional hetero-junction filler with a 1D-2D-1D feature, achieved by manipulating 2D graphene into 1D carbon fibers in the fiber-extruding process under the electric field. The as-fabricated 1D-2D-1D structural fillers exhibited much-improved dielectric properties and promoted microwave absorption performance in their composites, which is linked to the establishment of enhanced polarization capability, the generation of increased electric loss pathway and the creation of more favorable electromagnetic energy consumption conditions. The results suggest that employing 2D graphene in the 1D-2D-1D nanostructures played the critical role in tuning the electromagnetic response ability, because of its intrinsic electric advantages and dimensional features. To broaden the effective absorption bandwidth, periodic pattern-absorbing structures were designed, which showed combined absorption advantages for various thicknesses. Our strategy for fabricating 1D-2D-1D structural fillers illuminates a universal approach for manipulating dimensions and structures in the nanotechnology.

Cocaine blocks plasma membrane monoamine transporters and increases extracellular levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT). The addictive properties of cocaine are mediated primarily by DA, while NE and 5-HT play modulatory roles. Chronic inhibition of dopamine β-hydroxylase (DBH), which converts DA to NE, increases the aversive effects of cocaine and reduces cocaine use in humans, and produces behavioral hypersensitivity to cocaine and D2 agonism in rodents, but the underlying mechanism is unknown. We found a decrease in β-arrestin2 (βArr2) in the nucleus accumbens (NAc) following chronic genetic or pharmacological DBH inhibition, and overexpression of βArr2 in the NAc normalized cocaine-induced locomotion in DBH knockout (Dbh -/-) mice. The D2/3 agonist quinpirole decreased excitability in NAc medium spiny neurons (MSNs) from control, but not Dbh -/- animals, where instead there was a trend for an excitatory effect. The Gαi inhibitor NF023 abolished the quinpirole-induced decrease in excitability in control MSNs, but had no effect in Dbh -/- MSNs, whereas the Gαs inhibitor NF449 restored the ability of quinpirole to decrease excitability in Dbh -/- MSNs, but had no effect in control MSNs. These results suggest that chronic loss of noradrenergic tone alters behavioral responses to cocaine via decreases in βArr2 and cellular responses to D2/D3 activation, potentially via changes in D2-like receptor G-protein coupling in NAc MSNs.

This paper reports the visible luminescence properties of 1D2 state of Tm 3 + -doped lead borate titanate aluminumfluoride (LBTAFTm) glasses. The absorption and luminescence was analyzed within the frame work of Judd-Ofelt model. The reliability of J-O intensity parameters obtained from the experimental oscillator strengths have satisfactorily been correlated with the calculated oscillator strengths with small r.m.s deviation of ± 0.12 × 10 -6 by the least square fit analysis. Upon 359 nm excitation, the luminescence spectra show only one emission band at 458 nm (blue) corresponding to the 1D2 → 3 F 4 transition in the spectral region 400-500 nm. No luminescence quenching has been observed with the increase of Tm 3 + concentration. The decay profiles of the 1D2 level have shown single-exponential nature for all the concentrations and the decay times were found to decrease with the increase of concentration. The stimulated emission cross-section ( σe) for the observed emission transition has also been computed. The large quantum efficiency (η) of the 1D2 level suggests the utility of LBTAFTm glass as a potential host for optical device applications at 458 nm emission wavelength.

Full Text Available Salmonella enterica serovar Typhimurium is a Gram-negative bacterial pathogen causing gastroenteritis in humans and a systemic typhoid-like illness in mice. The capacity of Salmonella to cause diseases relies on the establishment of its intracellular replication niche, a membrane-bound compartment named the Salmonella-containing vacuole (SCV. This requires the translocation of bacterial effector proteins into the host cell by type three secretion systems. Among these effectors, SifA is required for the SCV stability, the formation of Salmonella-induced filaments (SIFs and plays an important role in the virulence of Salmonella. Here we show that the effector SopD2 is responsible for the SCV instability that triggers the cytoplasmic release of a sifA(- mutant. Deletion of sopD2 also rescued intra-macrophagic replication and increased virulence of sifA(- mutants in mice. Membrane tubular structures that extend from the SCV are the hallmark of Salmonella-infected cells. Until now, these unique structures have not been observed in the absence of SifA. The deletion of sopD2 in a sifA(- mutant strain re-established membrane trafficking from the SCV and led to the formation of new membrane tubular structures, the formation of which is dependent on other Salmonella effector(s. Taken together, our data demonstrate that SopD2 inhibits the vesicular transport and the formation of tubules that extend outward from the SCV and thereby contributes to the sifA(- associated phenotypes. These results also highlight the antagonistic roles played by SopD2 and SifA in the membrane dynamics of the vacuole, and the complex actions of SopD2, SifA, PipB2 and other unidentified effector(s in the biogenesis and maintenance of the Salmonella replicative niche.

Full Text Available Context Whether adjuvant chemoradiotherapy may contribute to improve survival outcomes after D2-gastrectomy remains controvertial. Objective To explore the clinical utility of N-Ratio in selecting gastric cancer patients for adjuvant chemoradiotherapy after D2-gastrectomy. Methods A retrospective cohort study was carried out on gastric cancer patients who underwent D2-gastrectomy alone or D2-gastrectomy plus adjuvant chemoradiotherapy (INT-0116 protocol at the Hospital A. C. Camargo from September 1998 to December 2008. Statistical analysis were performed using multiple conventional methods, such as c-statistic, adjusted Cox's regression and stratified survival analysis. Results Our analysis involved 128 patients. According to c-statistic, the N-Ratio (i.e., as a continuous variable presented “area under ROC curve” (AUC of 0.713, while the number of metastatic nodes presented AUC of 0.705. After categorization, the cut-offs provide by Marchet et al. displayed the highest discriminating power – AUC value of 0.702. This N-Ratio categorization was confirmed as an independent predictor of survival using multivariate analyses. There also was a trend of better survival by adding of adjuvant chemoradiotherapy only for patients with milder degrees of lymphatic spread – 5-year survival of 23.1% vs 66.9%, respectively (HR = 0.426, 95% CI 0.150–1.202; P = 0.092. Conclusions This study confirms the N-Ratio as a tool to improve the lymph node metastasis staging in gastric cancer and suggests the cut-offs provided by Marchet et al. as the best way for its categorization after a D2-gastrectomy. In these settings, the N-Ratio appears a useful tool to select patients for adjuvant chemoradiotherapy, and the benefit of adding this type of adjuvancy to D2-gastrectomy is suggested to be limited to patients with milder degrees of lymphatic spread (i.e., NR2, 10%–25%.

-term depression. Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activity of analogs of D-Ser and GluN1 glycine site competitive antagonists at GluD2 receptors containing the lurcher mutation (GluD2(LC)), which promotes spontaneous channel activation. We identify...

Mosaic IDH1 mutations are described as the cause of metaphyseal chondromatosis with increased urinary excretion of D-2-hydroxyglutarate (MC-HGA), and mutations in IDH2 as the cause of D-2-hydroxyglutaric aciduria (D-2HGA) type II. Mosaicism for IDH2 mutations has not previously been reported as a...

pharmacologically related to the D2 family. In the European eel, two distinct D2 receptor (D2‐R) paralogous genes have been identified (D2A‐R and D2B‐R) and both were shown to be expressed in the pituitary. We investigated the potential role of each paralogue in the control of gonadotroph function in this species....... Eel recombinant D2A‐R or D2B‐R were expressed in HEK 293 cells, with a universal Gα subunit, and receptor activation was followed by inositol phosphate production. Recombinant D2‐Rs exhibited a comparable affinity for DA, although they had differential affinities for mammalian D2‐R agonists...... and antagonists, supporting subtle structure/activity differences. Furthermore, using eel pituitary cell primary cultures, the expression by gonadotroph cells of both native eel D2‐R paralogues was examined by in situ hybridisation of D2A‐R or D2B‐R transcripts, coupled with immunofluorescence of luteinising...

We study three dimensional N=2 supersymmetric Chern-Simons-Matter theories on the direct product of circle and two dimensional hemisphere (S^1 x D^2) with specified boundary conditions by the method of localization. We construct boundary interactions to cancel the supersymmetric variation of three dimensional superpotential term and Chern-Simons term and show inflows of bulk-boundary anomalies. It finds that the boundary conditions induce two dimensional N=(0,2) type supersymmetry on the boundary torus. We also study the relation between the 3d-2d coupled partition function of our model and three dimensional holomorphic blocks.

In Direct Device-to-Device (D2D), the device awareness procedure known as the discovery phase is required prior to the exchange of data. This work considers autonomous devices where the infrastructure is not involved in the discovery procedure. Commonly, the transmission of the discovery message...... technology to provide D2D fast discovery. Such framework provides an algorithm to estimate the number of neighbor devices and to dynamically decide the transmission probability, for adapting to network changes and meeting the 10 milliseconds target. Finally, a signaling scheme is proposed to reduce...

In order to evaluate the effects of dietary addition of probiotic strain Lactobacillus acidophilus D2/CSL on hen performance and egg quality, 160 commercial Hy-Line Brown pullets, 17 weeks old, were divided in control group (C) (N=80) and treated group (T) (N=80), with 4 alternate replicates of 20 animals each per group. C was fed with a “standard diet”, whereas the T group received the same diet with an inclusion of 1x109 CFU kg-1 of Lactobacillus acidophilus D2/CSL (freeze dried...

Dual dopamine D2/5-HT2A receptor antagonists have potent activity and are referred to atypical antipsychotics due to their lower propensity to elicit EPS and their moderate efficacy toward negative symptoms. However, an on-going challenge in developing atypical antipsychotics drugs is to maintain the favorable profiles and avoid of cardiovascular risk. In this paper, comparative pharmacophore analysis of dual dopamine D2/5-HT2A receptor antagonists, hERG K+ channel blockers, and alA adrenoceptor antagonists is carried out, and the results could give some insight into multi-target drug design.

In the presence of linearly varying frequency chirped laser pulses the photodissociation dynamics of D$_2^+$ is studied theoretically after ionization of D$_{2}$ . As a completion of our recent work (J. Chem. Phys. 143, 014305 (2015)) a comprehensive dependence on the pulse duration and delay time is presented in terms of total dissociation probabilities. Our numerical analysis carried out in the recently introduced light-induced conical intersection (LICI) framework clearly shows the effects of the changing position of the LICI which is induced by the frequency modulation of the chirped laser pulses. This impact is presented for positively, negatively and zero chirped short pulses.

Adolescence is a developmental period characterized by heightened vulnerability to illicit drug use and the onset of neuropsychiatric disorders. These clinical phenomena likely share common neurobiological substrates, as mesocorticolimbic dopamine systems actively mature during this period. Whereas prior studies have examined age-dependent changes in dopamine receptor binding, there have been fewer functional analyses. The aim of the present study was therefore to determine whether the functional consequences of D1 and D2-like activation are age-dependent. Adolescent and adult rats were given direct D1 and D2 agonists, alone and in combination. Locomotor and stereotypic behaviors were measured, and brains were collected for analysis of mRNA expression for the immediate early genes (IEGs), cfos and arc. Adolescents showed enhanced D2-like receptor control of locomotor and repetitive behaviors, which transitioned to dominant D1-like mechanisms in adulthood. When low doses of agonists were co-administered, adults showed supra-additive behavioral responses to D1/D2 combinations, whereas adolescents did not, which may suggest age differences in D1/D2 synergy. D1/D2-stimulated IEG expression was particularly prominent in the bed nucleus of the stria terminalis (BNST). Given the BNST’s function as an integrator of corticostriatal, hippocampal, and stress-related circuitry, and the importance of neural network dynamics in producing behavior, an exploratory functional network analysis of regional IEG expression was performed. This data-driven analysis demonstrated similar developmental trajectories as those described in humans and suggested that dopaminergic drugs alter forebrain coordinated gene expression age dependently. D1/D2 recruitment of stress nuclei into functional networks was associated with low behavioral output in adolescents. Network analysis presents a novel tool to assess pharmacological action, and highlights critical developmental changes in functional

Arylcycloalkylamines, such as phenyl piperidines and piperazines and their arylalkyl substituents, constitute pharmacophoric groups exemplified in several antipsychotic agents. A review of previous reports indicates that arylalkyl substituents can improve the potency and selectivity of the binding affinity at D(2)-like receptors. In this paper, we explored the contributions of two key pharmacophoric groups, that is, 4'-fluorobutyrophenones and 3-methyl-7-azaindoles, to the potency and selectivity of synthesized agents at D(2)-like receptors. Preliminary observation of binding affinities indicates that there is little predictability of specific effects of the arylalkyl moieties but the composite structure is responsible for selectivity and potency at these receptors.

Full Text Available The total synthesis of the endogenous inflammation resolving eicosanoid resolvin D2 (1 is described. The key steps involved a Wittig reaction between aldehyde 5 and the ylide derived from phosphonium salt 6 to give enyne 17 and condensation of the same ylide with aldehyde 7 to afford enyne 11. Desilylation of 11 followed by hydrozirconation and iodination gave the vinyl iodide 4 and Sonogashira coupling between this compound and enyne 3 provided alkyne 18. Acetonide deprotection, partial reduction and ester hydrolysis then gave resolvin D2 (1.

It discusses the hybrid cellular network based on D2D communication, application scenarios and system requirements. It also discusses the implementation of LTE-D2D, analyzes the impact on network evolution and business model.%阐述了以端到端直通通信（D2D）为代表的混合蜂窝网络技术及应用场景、系统需求，探讨了LTE-D2D实现方案，分析了D2D对蜂窝网络和现商业模式的冲击。

Synthesis of a C-24-epimeric mixture of 25-hydroxy-(26,27-/sup 3/H)vitamin D2 and a C-24-epimeric mixture of 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 by the Grignard reaction of the corresponding 25-keto-27-nor-vitamin D2 and 1 alpha-acetoxy-25-keto-27-nor-vitamin D3 with tritiated methyl magnesium bromide is described. Separation of epimers by high-performance liquid chromatography afforded pure radiolabeled vitamins of high specific activity (80 Ci/mmol). The identities and radiochemical purities of 25-hydroxy-(26,27-/sup 3/H(vitamin D2 and 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2D2 were established by cochromatography with synthetic 25-hydroxyvitamin D2 or 1,25-dihydroxyvitamin D2. Biological activity of 25-hydroxy-(26,27-/sup 3/H)vitamin D2 was demonstrated by its binding to the rat plasma binding protein for vitamin D compounds, and by its in vitro conversion to 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 by kidney homogenate prepared from vitamin D-deficient chickens. The biological activity of 1,25-dihydroxy-(26,27-/sup 3/H)vitamin D2 was demonstrated by its binding to the chick intestinal receptor for 1,25-dihydroxyvitamin D3.

As for the systematic investigations of magnetic behaviors and its related properties, computer simulations in extended quantum spin networks have been performed in good conditions via the generalized Ising model using the Monte Carlo-Metropolis algorithm with proven efficiencies. The present work, starting from a real magnetic system, provides detailed insights into the finite size effects and the ferrimagnetic properties in various 1 D, 2D and 3D geometries such as the magnetic moment, ordering temperature, and magnetocaloric effects with the different values of spins localized on the different coordinated sites.

Endovascular image-guided interventions (EIGI) involve navigation of a catheter through the vasculature followed by application of treatment at the site of anomaly using live 2D projection images for guidance. 3D images acquired prior to EIGI are used to quantify the vascular anomaly and plan the intervention. If fused with the information of live 2D images they can also facilitate navigation and treatment. For this purpose 3D-2D image registration is required. Although several 3D-2D registration methods for EIGI achieve registration accuracy below 1 mm, their clinical application is still limited by insufficient robustness or reliability. In this paper, we propose a 3D-2D registration method based on matching a 3D vasculature model to intensity gradients of live 2D images. To objectively validate 3D-2D registration methods, we acquired a clinical image database of 10 patients undergoing cerebral EIGI and established "gold standard" registrations by aligning fiducial markers in 3D and 2D images. The proposed method had mean registration accuracy below 0.65 mm, which was comparable to tested state-of-the-art methods, and execution time below 1 s. With the highest rate of successful registrations and the highest capture range the proposed method was the most robust and thus a good candidate for application in EIGI.

The full D2.4 confidential deliverable describes the ecoDriver project’s key projected results and the plans for exploiting them. This public version omits the chapters on expoitoitable results and the project partners plans for exploiting them. This is the third year version of the deliverable repo

Objectives: A hybrid physiology-based pharmacokinetic and pharmacodynamic model (PBPKPD) was used to predict the time course of dopamine receptor occupancy (D2RO) in human striatum following the administration of antipsychotic (AP) drugs, using in vitro and in silico information. Methods: A hybrid P

Full Text Available Recent reports have shown that cannabinoid 1 receptors (CB1Rs are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212-2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes.

Synaptic plasticity, such as long-term potentiation and long-term depression (LTD), is believed to underlie learning and memory processes in vivo. The cerebellum is an ideal brain region to obtain definitive proof for this hypothesis. The current belief is that the acquisition of motor learning is stored by LTD at the parallel fiber (PF)-Purkinje cell synapse in the cerebellar cortex. Recently, however, several lines of mutant mice that display normal motor learning in the absence of cerebellar LTD have been reported. A similar dichotomy between synaptic plasticity at the circuitry level and learning at the behavioral level has also been reported in the hippocampus. One possible explanation for this dichotomy is that compensatory pathways at the molecular and circuitry levels play an important role in mice that have been genetically modified for their entire lives. Mice that are genetically modified to be deficient in or to express mutant versions of the δ2 glutamate receptor (GluD2) serve as an interesting model due to the predominant expression of GluD2 at PF-Purkinje cell synapses. Furthermore, two major functions of GluD2-PF synapse formation and LTD induction-can be mechanistically dissociated so that the role of LTD in motor learning can be investigated in the absence of morphological abnormalities caused by altered synapse formation. Therefore, genetic manipulations of GluD2 will help to clarify the relationship between LTD and motor learning in the cerebellum.

The solvent extraction of copper and zinc from the bioleaching solutions of low-grade sulfide ores with LIX984 and D2EHPA was investigated. The influences of extractant content, aqueous pH value, phase ratio and equilibration time on metals extraction were studied. The results show that LIX984 has a higher selectivity for copper than for iron, zinc and other metals, and has the copper extraction rate above 97%,while the zinc and iron extraction rate is less than 1.6% respectively. Zinc extraction is carried out following the copper extraction from the raffinate. The zinc extraction with di(2-ethylhexyl) phosphoric acid(D2EHPA) is low due to its poor cation exchange. A sodium salt of D2EHPA is used and the zinc extraction rate is enhanced to above 98%. Though iron (Ⅲ) is strongly extracted before the extraction of zinc by D2EHPA, it is difficult to strip iron from the organic phase by sulfuric acid. The zinc stripping rate is above 99% with 100 g/L sulfuric acid, while that of iron is 0.16%. Hence, the separation of zinc from iron can be achieved by the selective stripping.

In this paper we investigate the quality of 3D-2D pose estimates using hand labeled line and point correspondences. We select point correspondences from junctions in the image, allowing to construct a meaningful interpretation about how the junction is formed, as proposed in e.g. [1], [2], [3]. We...

The demonstration described in this article is to show thatwhile H$_2$O ice floats in water, D$_2$O ice sinks in water, provingthe higher density of ‘heavy water’. This experiment can bedone in a classroom or in an auditoriam.

Recent studies suggest an association of dopamine D2 receptor (DRD2) availability with flexibility in reward-based learning. We extend these results by demonstrating an association of genetically based differences in DRD2 density with the ability to intentionally switch between nonrewarded tasks:

This thesis describes the bioanalysis and pharmacokinetics of the S(-) enantiomer (N-0923) of the selective and potent dopamine D2 agonist 2-(N-propyl-N-2-thienylethyl-amino)-5-hydroxytetralin, N-0437 which has possible applications in the treatment of Parkinson’s disease. The R(+) enantiomer

the target for the complementary needs of certain fundamental physics experiments. To facilitate experiments depending on the total number of neutrons in a sizable beam, the option of a voluminous D2 moderator, in a large cross-section extraction guide is discussed and its neutronic performance is assessed....

The kinetic-energy distribution of D+ fragments obtained from the ionization of D2 molecules with intense 20-fs pulses includes a high-energy component extending up to ˜10 eV. These fragments are only present for linearly, or slightly elliptically, polarized light. Both the maximum kinetic...

The objective of this project was to perform thermal loading simulations of TCDXM (D2 collimator mask) and TAXN so as to allow the preliminary evaluation of the suitability of the given parts for the upcoming high luminosity upgrade that is to be performed in LHC in the nearest future.

In this paper we investigate the quality of 3D-2D pose estimates using hand labeled line and point correspondences. We select point correspondences from junctions in the image, allowing to construct a meaningful interpretation about how the junction is formed, as proposed in e.g. [1], [2], [3]. We...

We report on the results of the E06-014 experiment performed at Jefferson Lab in Hall A, where a precision measurement of the twist-3 matrix element $d_2$ of the neutron ($d_{2}^{n}$) was conducted. This quantity represents the average color Lorentz force a struck quark experiences in a deep inelastic electron scattering event off a neutron due to its interaction with the hadronizing remnants. This color force was determined from a linear combination of the third moments of the spin structure functions $g_1$ and $g_2$ on $^{3}$He after nuclear corrections had been applied to these moments. The kinematics included two average $Q^{2}$ bins of $3.2$ GeV$^{2}$ and $4.3$ GeV$^{2}$, and Bjorken-$x$ $0.25 \\leq x \\leq 0.90$ covering the DIS and resonance regions. We found $d_2^n$ to be small and negative for $ = 3.2$ GeV$^{2}$, and smaller for $ = 4.3$ GeV$^{2}$, consistent with a lattice QCD calculation. The twist-4 matrix element $f_{2}^{n}$ was extracted by combining our $d_{2}^{n}$ with the world data on $\\Gamma_...

AIMS™ Die-to-Die (D2D) is widely used in checking the wafer printability of mask defects for DUV lithography. Two AIMS images, a reference and a defect image, are captured and compared with differences larger than certain tolerances identified as real defects. Since two AIMS images are needed, and since AIMS system time is precious, it is desirable to save image search and capture time by simulating reference images from the OPC mask pattern and AIMS optics. This approach is called Die-to-Database (D2DB). Another reason that D2DB is desirable is in single die mask, where the reference image from another die does not exist. This paper presents our approach to simulate AIMS optics and mask 3D effects. Unlike OPC model, whose major concern is predicting printed CD, AIMS D2DB model must produce simulated images that match measured images across the image field. This requires a careful modeling of all effects that impact the final image quality. We present a vector-diffraction theory that is based on solid theoretical foundations and a general formulation of mask model that are applicable to both rigorous Maxwell solver and empirical model that can capture the mask 3D-effects. We demonstrated the validity of our approach by comparing our simulated image with AIMS machine measured images. We also briefly discuss the necessary changes needed to model EUV optics. Simulation is particularly useful while the industry waits for an actinic EUV-AIMS tool.

The emission of secondary electrons from solid hydrogen (H2 , D2, T2) is often considered to be of importance for the interaction between a fusion plasma and pellets of solid hydrogens. A set-up was therefore built for studies of interactions between energetic particles and solid hydrogens. Studies...

Full Text Available We study the coordinated precoding problem for device-to-device (D2D communications underlay multiple-input multiple-output (MIMO cellular networks. The system model considered here constitutes multiple D2D user pairs attempting to share the uplink radio resources of a cellular network. We first formulate the coordinated precoding problem for the D2D user pairs as a sum-rate maximization (SRM problem, which is subject to a total interference power constraint imposed to protect the base station (BS and individual transmit power budgets available for each D2D user pair. Since the formulated SRM problem is nonconvex in general, we reformulate it as a difference convex- (DC- type programming problem, which can be iteratively solved by employing the famous successive convex approximation (SCA method. Moreover, a proximal-point-based regularization approach is also pursued here to ensure the convergence of the proposed algorithm. Interestingly, the centralized precoding algorithm can also lend itself to a distributed implementation. By introducing a price-based interference management mechanism, we reformulate the coordinated precoding problem as a Stackelberg game. Then, a distributed precoding algorithm is developed based on the concept of Stackelberg equilibrium (SE. Finally, numerical simulations are also provided to demonstrate the proposed algorithms. Results show that our algorithms can converge fast to a satisfactory solution with guaranteed convergence.

We use the Fourier based Gabetta-Toscani-Wennberg metric d_2 to study the rate of convergence to equilibrium for the Kac model in 1 dimension. We take the initial velocity distribution of the particles to be a Borel probability measure μ on R^n that is symmetric in all its variables, has mean ěc {0} and finite second moment. Let μ _t(dv) denote the Kac-evolved distribution at time t, and let R_μ be the angular average of μ . We give an upper bound to d_2(μ _t, R_μ ) of the form \\min { B e^{-4 λ _1/n+3t}, d_2(μ ,R_μ )} , where λ _1 = n+2/2(n-1) is the gap of the Kac model in L^2 and B depends only on the second moment of μ . We also construct a family of Schwartz probability densities {f_0^{(n)}: R^n→ R} with finite second moments that shows practically no decrease in d_2(f_0(t), R_{f_0}) for time at least 1/2λ with λ the rate of the Kac operator. We also present a propagation of chaos result for the partially thermostated Kac model in Tossounian and Vaidyanathan (J Math Phys 56(8):083301, 2015).

OBJECTIVE: Prostaglandin D2 (PGD2) may exert proinflammatory or antiinflammatory effects in different biologic systems. Although this prostanoid and the enzymes responsible for its synthesis are up-regulated by interleukin-1beta (IL-1beta) in human chondrocytes in vitro, the role of PGD2 in arthriti

We present a non-linear representation of the so(4)-extended d=2 superconformal algebra in terms of one boson and four Majorana fermions. The matter fields and the currents can be grouped into a single N=4 superfield. Breaking the supersymmetry to N=3 or N=2 leads to new representations of the N=3,2

An extensive survey of the D-2 absorption spectrum has been performed with the high-resolution VUV Fourier-transform spectrometer employing synchrotron radiation. The frequency range of 90 000-119 000 cm (1) covers the full depth of the potential wells of the B (1)Sigma(+)(u), B' 1 Sigma(+)(u), and

Deviations in reward sensitivity and behavioral flexibility, particularly in the ability to change or stop behaviors in response to changing environmental contingencies, are important phenotypic dimensions of several neuropsychiatric disorders. Neuroimaging evidence suggests that variation in dopamine signaling through dopamine D(2)-like receptors may influence these phenotypes, as well as associated psychiatric conditions, but the specific neurocognitive mechanisms through which this influence is exerted are unknown. To address this question, we examined the relationship between behavioral sensitivity to reinforcement during discrimination learning and D(2)-like receptor availability in vervet monkeys. Monkeys were assessed for their ability to acquire, retain, and reverse three-choice, visual-discrimination problems, and once behavioral performance had stabilized, they received positron emission tomography (PET) scans. D(2)-like receptor availability in dorsal aspects of the striatum was not related to individual differences in the ability to acquire or retain visual discriminations but did relate to the number of trials required to reach criterion in the reversal phase of the task. D(2)-like receptor availability was also strongly correlated with behavioral sensitivity to positive, but not negative, feedback during learning. These results go beyond electrophysiological findings by demonstrating the involvement of a striatal dopaminergic marker in individual differences in feedback sensitivity and behavioral flexibility, providing insight into the neural mechanisms that are affected in neuropsychiatric disorders that feature these deficits.

Though the dopaminergic system is implicated in Obsessive Compulsive and Related Disorders (OCRD), the dopaminergic system has never been investigated in-vivo in Body Dysmorphic Disorder (BDD). In line with consistent findings of reduced striatal dopamine D2/3 receptor availability in Obsessive

Full Text Available With the current development of mobile communication services, people need personal communication of high speed, excellent service, high quality and low latency，however, limited spectrum resources become the most important factor to hamper improvement of cellular systems. As big amount of data traffic will cause greater local consumption of spectrum resources, future networks are required to have appropriate techniques to better support such forms of communication. D2D (Device-to-device communication technology in a cellular network makes full use of spectrum resources underlaying, reduces the load of the base station, minimizes transmit power of the terminals and the base stations, thereby enhances the overall throughput of the networks. Due to the use of multiplexing D2D UE (User equipment resources and spectrum, and the interference caused by the sharing of resources between adjacent cells, it has become a major factor affecting coexisting of cellular subscribers and D2D users. When D2D communication multiplexes the uplink resources, the base-stations are easily to be disturbed; when the downlink resources are multiplexed, the users of downlink are susceptible to interference. In order to build a high-efficient mobile network, we can meet the QoS requirements by controlling the power to suppress the interference between the base station and a terminal user.

The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa.

Wireless cellular networks feature two emerging technological trends: direct Device-to-Device (D2D) communications and Machine-Type Communications (MTC). MTC devices (MTDs) pose new challenges to the cellular network, such as low transmission power and massive access that can lead to overload...

The emission of secondary electrons from solid hydrogen (H2 , D2, T2) is often considered to be of importance for the interaction between a fusion plasma and pellets of solid hydrogens. A set-up was therefore built for studies of interactions between energetic particles and solid hydrogens. Studi...

We discuss recent experiments involving ultracold strontium. Using a commercially-available 3 micron laser, we repump atoms out of the ^3P2 level via the ^3D2 state and gain almost a factor of 10 in the number of atoms in our system. This increase in the signal-to-noise ratio enables improved spectroscopy of strontium in our optical trap.

We report on the results of the E06-014 experiment performed at Jefferson Lab in Hall A, where a precision measurement of the twist-3 matrix element d2 of the neutron (d2n) was conducted. The quantity d2n represents the average color Lorentz force a struck quark experiences in a deep inelastic electron scattering event off a neutron due to its interaction with the hadronizing remnants. This color force was determined from a linear combination of the third moments of the 3He spin structure functions, g1 and g2, after nuclear corrections had been applied to these moments. The structure functions were obtained from a measurement of the unpolarized cross section and of double-spin asymmetries in the scattering of a longitudinally polarized electron beam from a transversely and a longitudinally polarized 3He target. The measurement kinematics included two average Q2 bins of 3.2 GeV2 and 4.3 GeV2 , and Bjorken-x 0.25 ≤x ≤0.90 covering the deep inelastic and resonance regions. We have found that d2n is small and negative for ⟨Q2⟩ =3.2 GeV2 , and even smaller for ⟨Q2⟩ =4.3 GeV2 , consistent with the results of a lattice QCD calculation. The twist-4 matrix element f2n was extracted by combining our measured d2n with the world data on the first moment in x of g1n, Γ1n. We found f2n to be roughly an order of magnitude larger than d2n. Utilizing the extracted d2n and f2n data, we separated the Lorentz color force into its electric and magnetic components, FEy ,n and FBy ,n, and found them to be equal and opposite in magnitude, in agreement with the predictions from an instanton model but not with those from QCD sum rules. Furthermore, using the measured double-spin asymmetries, we have extracted the virtual photon-nucleon asymmetry on the neutron A1n, the structure function ratio g1n/F1n, and the quark ratios (Δ u +Δ u ¯)/(u +u ¯) and (Δ d +Δ d ¯)/(d +d ¯). These results were found to be consistent with deep-inelastic scattering world data and with the

The loss of nigrostriatal dopamine neurons in Parkinson's disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson's disease.

Among the substances isolated from Cryptocarya sp, some styrylpyrones, such as goniothalamin, demonstrate antiproliferative activity in a broad range of human cell lines. In the present study, we assessed the cytotoxicity of a styrylpyrone (cryptomoschatone D2, isolated from Cryptocarya mandiocanna, in HPV-infected (HeLa and SiHa and uninfected (C33A human cervical carcinoma cell lines and a human lung fibroblast line (MRC-5. The cytotoxicity was tested by the MTT assay. In this assay, cells were treated with cryptomoschatone D2 at 15, 30, 60 or 90 μM for 6, 24 or 48 hours, as well as for 6 hours followed by a post-treatment recovery period of 24, 48 or 72 hours. High cytotoxicity (dose- and timedependent was observed in HeLa, SiHa, C33A and MRC-5 cell lines. Although in general the styrylpyrone cytotoxicity was not significantly different among the cell lines tested, it was apparently stronger in HeLa and C33A than in MRC-5 and SiHa in the 24 or 48-hour treatments. Moreover, HeLa and SiHa were able to recover their ability to proliferate, in direct proportion to the post-treatment recovery time. On the other hand, C33A did not demonstrate a similar post-treatment recovery. We can conclude that cryptomoschatone D2 possesses high dose-dependent or time-dependent cytotoxicity. Keywords: Cell culture. Antiproliferative activity. Styrylpyrone, Cryptomoschatone D2. RESUMO Cryptomoscatona D2 de Cryptocarya mandioccana: atividade citotóxica contra linhagem celular de carcinoma cervical humano Dentre as substâncias isoladas de Cryptocarya sp, algumas estirilpironas, como a goniotalamina, apresentam atividade antiproliferativa em diferentes linhagens celulares. No presente estudo, foram avaliadas as atividades citotóxica de uma estirilpirona (criptomoscatona D2 isolada de Cryptocarya mandiocanna, em linhagens celulares de carcinoma cervical humano infectada por HPV (HeLa e SiHa, não infectada (C33A e fibroblasto pulmonar humano

Striatal medium spiny neurons (MSNs) are contacted by glutamatergic axon terminals originating from cortex, thalamus and other regions. The striatum is also innervated by dopaminergic (DAergic) terminals, some of which release glutamate as a co-transmitter. Despite evidence for functional DA release at birth in the striatum, the role of DA in the establishment of striatal circuitry is unclear. In light of recent work suggesting activity-dependent homeostatic regulation of glutamatergic terminals on MSNs expressing the D2 DA receptor (D2-MSNs), we used primary co-cultures to test the hypothesis that stimulation of DA and glutamate receptors regulates the homeostasis of glutamatergic synapses on MSNs. Co-culture of D2-MSNs with mesencephalic DA neurons or with cortical neurons produced an increase in spines and functional glutamate synapses expressing VGLUT2 or VGLUT1, respectively. The density of VGLUT2-positive terminals was reduced by the conditional knockout of this gene from DA neurons. In the presence of both mesencephalic and cortical neurons, the density of synapses reached the same total, compatible with the possibility of a homeostatic mechanism capping excitatory synaptic density. Blockade of D2 receptors increased the density of cortical and mesencephalic glutamatergic terminals, without changing MSN spine density or mEPSC frequency. Combined blockade of AMPA and NMDA glutamate receptors increased the density of cortical terminals and decreased that of mesencephalic VGLUT2-positive terminals, with no net change in total excitatory terminal density or in mEPSC frequency. These results suggest that DA and glutamate signaling regulate excitatory inputs to striatal D2-MSNs at both the pre- and postsynaptic level, under the influence of a homeostatic mechanism controlling functional output of the circuit.

An algorithm for intensity-based 3D-2D registration of CT and C-arm fluoroscopy is evaluated for use in surgical guidance, specifically considering the low-dose limits of the fluoroscopic x-ray projections. The registration method is based on a framework using the covariance matrix adaptation evolution strategy (CMA-ES) to identify the 3D patient pose that maximizes the gradient information similarity metric. Registration performance was evaluated in an anthropomorphic head phantom emulating intracranial neurosurgery, using target registration error (TRE) to characterize accuracy and robustness in terms of 95% confidence upper bound in comparison to that of an infrared surgical tracking system. Three clinical scenarios were considered: (1) single-view image + guidance, wherein a single x-ray projection is used for visualization and 3D-2D guidance; (2) dual-view image + guidance, wherein one projection is acquired for visualization, combined with a second (lower-dose) projection acquired at a different C-arm angle for 3D-2D guidance; and (3) dual-view guidance, wherein both projections are acquired at low dose for the purpose of 3D-2D guidance alone (not visualization). In each case, registration accuracy was evaluated as a function of the entrance surface dose associated with the projection view(s). Results indicate that images acquired at a dose as low as 4 μGy (approximately one-tenth the dose of a typical fluoroscopic frame) were sufficient to provide TRE comparable or superior to that of conventional surgical tracking, allowing 3D-2D guidance at a level of dose that is at most 10% greater than conventional fluoroscopy (scenario #2) and potentially reducing the dose to approximately 20% of the level in a conventional fluoroscopically guided procedure (scenario #3).

Full Text Available Abstract Inactivation of the gene encoding the adenomatous polyposis coli (APC tumour suppressor protein is recognized as the key early event in the development of colorectal cancers (CRC. Apc loss leads to nuclear localization of beta-catenin and constitutive activity of the beta-catenin-Tcf4 transcription complex. This complex drives the expression of genes involved in cell cycle progression such as c-Myc and cyclin D2. Acute loss of Apc in the small intestine leads to hyperproliferation within the intestinal crypt, increased levels of apoptosis, and perturbed differentiation and migration. It has been demonstrated that c-Myc is a critical mediator of the phenotypic abnormalities that follow Apc loss in the intestine. As it may be difficult to pharmacologically inhibit transcription factors such as c-Myc, investigating more druggable targets of the Wnt-c-Myc pathway within the intestine may reveal potential therapeutic targets for CRC. Recent work in our laboratory has shown that the cyclin D2-cyclin-dependent kinase 4/6 (CDK4/6 complex promotes hyperproliferation in Apc deficient intestinal tissue and ApcMin/+ adenomas. We showed that the hyperproliferative phenotype associated with Apc loss in vivo was partially dependent on the expression of cyclin D2. Most importantly, tumour growth and development in ApcMin/+ mice was strongly perturbed in mice lacking cyclin D2. Furthermore, pharmacological inhibition of CDK4/6 suppressed the proliferation of adenomatous cells. This commentary discusses the significance of this work in providing evidence for the importance of the cyclin D2-CDK4/6 complex in colorectal adenoma formation. It also argues that inhibition of this complex may be an effective chemopreventative strategy in CRC.

Full Text Available The primary motor cortex (M1 is involved in fine voluntary movements control. Previous studies have shown the existence of a dopamine (DA innervation in M1 of rats and monkeys that could directly modulate M1 neuronal activity. However, none of these studies have described the precise distribution of DA terminals within M1 functional region nor have quantified the density of this innervation. Moreover, the precise role of DA on pyramidal neuron activity still remains unclear due to conflicting results from previous studies regarding D2 effects on M1 pyramidal neurons.In this study we assessed in mice the neuroanatomical characteristics of DA innervation in M1 using unbiased stereological quantification of dopamine transporter-immunostained fibers. We demonstrated for the first time in mice that DA innervates the deep layers of M1 targeting preferentially the forelimb representation area of M1. To address the functional role of the DA innervation on M1 neuronal activity, we performed electrophysiological recordings of single neurons activity in vivo and pharmacologically modulated D2 receptors activity. Local D2 receptors activation by quinpirole enhanced pyramidal neurons spike firing rate without changes in spike firing pattern. Altogether, these results indicate that DA innervation in M1 can increase neuronal activity through D2 receptors activation and suggest a potential contribution to the modulation of fine forelimb movement. Given the demonstrated role for DA in fine motor skill learning in M1, our results suggest that altered D2 modulation of M1 activity may be involved in the pathophysiology of movement disorders associated with disturbed DA homeostasis.

目的：本文探讨了包封于脂质体中的维生素D2体外透皮扩散能力的变化。方法：将维生素D2包封于脂质体中，并进一步制备成羧甲基纤维素钠的凝胶剂，与未包封于脂质体中的维生素D2的羧甲基纤维素钠凝胶剂比较，进行了大鼠离体皮肤的扩散实验，比较不同类型的脂质体对维生素D2透皮的影响。结果：维生素D2在游离状态下，不易进入皮肤层。维生素D2脂质体可使维生素D2在皮肤层中滞留，而且多室脂质体凝胶剂比单室脂质体凝胶剂在皮肤层中维生素D2的滞留量多。结论：脂质体作为维生素D2皮肤局部给药的载体，能够提高对皮肤的穿透力。%OBJECTIVE To investigate the changes of liposomal vitamin D2 inpermeability through the rat skin in vitro. METHODS The rat skin diffusion of liposomal vitamin D2 in carboxymethylcellulose-sodium gel dosage form through was compared with non-liposomal vitamin D2 in the gel dosage form in vitro. RESULTS The permeability of non-liposomal vitamin D2 through the rat skin was poor.When vitamin D2 entrapped in liposomes, the permeability of vitamin D2 through skin increased and deposited in skin. The multilamellar vesicles detained a higher amount of vitamin D2 than the unilamillar vesicles in skin. The amount of vitamin D2 in the receiver cell did not increase significantly.CONCLUSIONS Liposomes can be used as a carrier of vitamin D2 in topical application that increase the permeability through the rat skin.

The dopamine D2 receptor (D2R) negatively regulates inflammation in mouse renal proximal tubule cells (RPTCs), and lack or downregulation of the receptor in mice increases the vulnerability to renal inflammation independent of blood pressure. Some common single-nucleotide polymorphisms (SNPs; rs6276, rs6277, and rs1800497) in the human DRD2 gene are associated with decreased D2R expression and function, as well as high blood pressure. We tested the hypothesis that human RPTCs (hRPTCs) expressing these SNPs have increased expression of inflammatory and injury markers. We studied immortalized hRPTCs carrying D2R SNPs and compared them with cells carrying no D2R SNPs. RPTCs with D2R SNPs had decreased D2R expression and function. The expressions of the proinflammatory tumor necrosis factor-α and the profibrotic transforming growth factor-β1 and its signaling targets Smad3 and Snail1 were increased in hRPTC with D2R SNPs. These cells also showed induction of epithelial mesenchymal transition and production of extracellular matrix proteins, assessed by increased vimentin, fibronectin 1, and collagen I a1. To test the specificity of these D2R SNP effects, hRPTC with D2R SNPs were transfected with a plasmid encoding wild-type DRD2. The expression of D2R was increased and that of transforming growth factor-β1, Smad3, Snail1, vimentin, fibronectin 1, and collagen I a1 was decreased in hRPTC with D2R SNPs transfected with wild-type DRD2 compared with hRPTC-D2R SNP transfected with empty vector. These data support the hypothesis that D2R function has protective effects in hRPTCs and suggest that carriers of these SNPs may be prone to chronic renal disease and high blood pressure.

There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV......-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20–37-year-old women (n 33) in Helsinki (60°N) during winter (February–April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d......; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D...

Among the many additive manufacturing technologies, the directed energy deposition (DED) process has attracted significant attention because of the application of metal products. Metal deposited by the DED process has different properties than wrought metal because of the rapid solidification rate, the high thermal gradient between the deposited metal and substrate, etc. Additionally, many operating parameters, such as laser power, beam diameter, traverse speed, and powder mass flow rate, must be considered since the characteristics of the deposited metal are affected by the operating parameters. In the present study, the effect of energy input on the characteristics of H13 and D2 steels deposited by a direct metal tooling process based on the DED process was investigated. In particular, we report that the hardness of the deposited H13 and D2 steels decreased with increasing energy input, which we discuss by considering microstructural observations and thermodynamics.

There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (PD2 supplement was more effective than bread in increasing S-25(OH)D2 (PD2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (PD2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

D2 gastrectomy has been regarded as an inconvenient procedure with high morbidity and no survival benefit in the West. Recent studies, however, have shown low mortality and a survival benefit of D2 gastrectomy. In the Instituto de Enfermedades Neoplasicas (INEN) of Lima Peru D2 gastrectomy is performed since 1990 after training of some of the authors in the NCC of Tokyo Japan. Distal Pancreatectomy was performed only if the pancreas was involved.The aim of this study was to evaluate the peri operative mortality and survival in a group of patients who had a standard D2 lymphadenectomy according to the rules of the Japanese Research Society for Gastric Cancer. Data were collected prospectively, and patients were followed for more than 7 years. Between 1990 and 1999, 938 patients with localized gastric cancer were registered at INEN. Of these, 801 patients underwent curative resection with extended lymphadenectomy (D2). Postoperative morbidity/mortality, type of gastrectomy, mean of lymph nodes removed, pTNM stages and Survival Time and were analyzed. Sub total distal gastrectomy was performed in 511 patients and total gastrectomy in 290 patients. The mean number of lymph nodes removed was 46.48 per patient (54.91 nodes for total and 41.69 for sub total distal gastrectomy). Hospital mortality was 2.9%. 11% were Stage (TNM) IA, 9.4% stage IB, 19% stage II, 24.6% stage IIIA, 13.1% stage IIIB and 23% stage IV. Five-year actuarial survival was 47.5%. Five-year survival of patients with TNM stages IA, IB, II, IIIA, IIIB and IV were 85.8%, 79.4%, 60%, 46.7% 33% and 14.3% respectively. Gastrectomy with D2 lymphadenectomy may be performed with low morbidity and mortality if the operation is performed in specialized centers with a strict quality control system, and without removing the pancreas during total gastrectomy unless it is suspected to be involved. This procedure could provide a good probability of long-term survival, even for patients with invaded regional lymph

Full Text Available Recently, the Dynavision™ D2 Visuomotor Training Device (D2 has emerged as a tool in the assessment of reaction time (RT; however, information regarding the reliability of the D2 have been limited, and to date, reliability data have been limited to non- generalizable samples. Therefore, the purpose of this study was to establish intraclass correlation coefficients (ICC2,1 for the D2 that are generalizable across a population of recreationally active young adults. Forty-two recreationally active men and women (age: 23.41 ± 4.84 years; height: 1.72 ± 0.11 m; mass: 76.62 ± 18.26 Kg completed 6 trials for three RT tasks of increasing complexity. Each trial was separated by at least 48-hours. A repeated measures ANOVA was used to detect differences in performance across the six trials. Intraclass correlation coefficients (ICC2,1 standard error of measurement (SEM, and minimal differences (MD were used to determine the reliability of the D2 from the two sessions with the least significant difference score. Moderate to strong reliability was demonstrated for visual RT (ICC2,1: 0.84, SEM: 0.033, and reactive ability in both Mode A and Mode B tasks (Mode A hits: ICC2,1: 0.75, SEM: 5.44; Mode B hits: ICC2,1: 0.73, SEM: 8.57. Motor RT (ICC2,1: 0.63, SEM: 0.035s showed fair reliability, while average RT per hit for Modes A and B showed moderate reliability (ICC2,1: 0.68, SEM: 0.43 s and ICC2,1: 0.72, SEM: 0.03 s respectively. It appears that one familiarization trial is necessary for the choice reaction time (CRT task while three familiarization trials are necessary for reactive RT tasks. In conclusion, results indicate that the Dynavision™ D2 is a reliable device to assess neuromuscular reactivity given that an adequate practice is provided. The data presented are generalizable to a population of recreationally active young adults.

While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [(11)C]-raclopride in 30 healthy humans. Based on previous the literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions.

The anatomical proximity of the cannabinoid type 1 (CNR1/CB1R) and the dopamine D2 receptors (DRD2), their ability to form CB1R-DRD2 heteromers, their opposing roles in locomotion, and their involvement in ethanol's reinforcing and addictive properties prompted us to study the levels and distribution of CB1R after chronic ethanol intake, in the presence and absence of DRD2. We monitored the drinking patterns and locomotor activity of Drd2+/+ and Drd2-/- mice consuming either water or a 20% (v/v) ethanol solution (forced ethanol intake) for 6 months and used the selective CB1 receptor antagonist [{sup 3}H]SR141716A to quantify CB1R levels in different brain regions with in vitro receptor autoradiography. We found that the lack of DRD2 leads to a marked upregulation (approximately 2-fold increase) of CB1R in the cerebral cortex, the caudate-putamen, and the nucleus accumbens, which was reversed by chronic ethanol intake. The results suggest that DRD2-mediated dopaminergic neurotransmission and chronic ethanol intake exert an inhibitory effect on cannabinoid receptor expression in cortical and striatal regions implicated in the reinforcing and addictive properties of ethanol.

Full Text Available Abstract Dopamine dysregulation syndrome (DDS consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson’s disease (PD. Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

3D-2D registration is a fundamental task in image guided interventions. Due to the physics of the X-ray imaging, however, traditional point based methods meet new challenges, where the local point features are indistinguishable, creating difficulties in establishing correspondence between 2D image feature points and 3D model points. In this paper, we propose a novel method to accomplish 3D-2D registration without known correspondences. Given a set of 3D and 2D unmatched points, this is achieved by introducing correspondence probabilities that we model as a mixture model. By casting it into the expectation conditional maximization framework, without establishing one-to-one point correspondences, we can iteratively refine the registration parameters. The method has been tested on 100 real X-ray images. The experiments showed that the proposed method accurately estimated the rotations (< 1°) and in-plane (X-Y plane) translations (< 1 mm).

Secondary electron emission from solid HD and a solid 0.6 H2 + 0.4 D2 mixture has been studied for electron and hydrogen ion bombardment at primary energies from 0.5 to 3 keV and 2 to 10 keV/amu, respectively. The yield for solid HD is well explained by a simple stoichiometric model of the low......-energy stopping power for the internal secondaries. The secondary electron yield from the mixture is somewhat larger than the expected value, but lies between the values for pure solid H2 and D2. The secondary electron emission coefficient for solid tritium may be determined from a linear extrapolation...... of the present data....

The aziridinium ion of ethylcholine (AF64A) is a neurotoxin that has demonstrated selectivity for cholinergic neurons. Unilateral stereotaxic injection of AF64A into the caudate-putamen of rats, resulted in a decrease in dopamine D-2 receptors as evidenced by a decrease in (/sup 3/H)-sulpiride binding. Dopamine D-1 receptors, labeled with (/sup 3/H)-SCH 23390, were unchanged. The efficacy of the lesion was demonstrated by the reduction of Na/sup +/-dependent high affinity choline uptake sites labeled with (/sup 3/H)-hemicholinium-3. These data indicate that a population of D-2 receptors are postsynaptic on cholinergic interneurons within the striatum of rat brain.

We demonstrate the guiding of a supersonic heavy-water(D2O)molecular beam using a hollow electrostatic field generated by the combination of two parallel charged-wires and two grounded metal-plates,and report some new and preliminary experimental results.In the experiment,we detect the guiding signals by using the method of time-of-flight mass spectrum and study the dependence of the relative transmission of the beam guide on the guiding voltage.Our study shows that the relative transmission of the beam guide is increased linearly with increasing guiding voltage Vguid,and the number of the guided D2O molecules is at least increased by 89.4%when the guiding voltage is +20.0kV.Finally,some potential applications of our guiding scheme in the molecule optics are briefly discussed.

The synthesis and characterization of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug, are described. 3,4,6-Tri-O-benzyl-alpha-D-2-deoxyglucopyranose was synthesized by methylating the anomeric hydroxyl group of 2-deoxyglucose, benzylating the 3-, 4-, and 6-hydroxy functional grups, and cleaving hydrolytically the anomeric methyl group. Reaction of the tribenzylated sugar with the acid chloride of aspirin and subsequent hydrogenolysis of the benzyl groups resulted in the prodrug, mp 128 degrees. The compound was further characterized by elemental analysis and PMR and 13C-NMR spectroscopy. In vitro, the compound cleaved to aspirin with a half-life of 7 min at 37 degrees. Prodrug cleavage was independent of pH over the pH 3--9 range.

A fusion method of Gabor features and (2D)2LDA for face feature extraction is proposed in this paper. Gabor filters are utilized to extract multi⁃direction and multi⁃scale features from facial image to employ its robust performance for illumination, expressional variability and other factors. The extracted features have the defect of high dimension and redundancy data. (2D)2LDA is implemented to reduce the dimension of Gabor features and select effective feature data. Finally, the nearest neighbor classifier is used to classify characteristics and complete face recognition. The experiments are implemented by using ORL database and Yale database respectively. The experimental results show that the proposed method significantly reduces the dimension of Gabor features and decrease the influence of other factors. The proposed method acquires excellent recognition accuracy and has light architectures as well.

Full Text Available This study shows the effect of heat treatment on the torsion aspects of D2 alloy steel, in addition further analysis using ANSYS11 software w as used in investigation. Test specimens were prepared using high accurate machines (CNC however, hardening at different austenite temperature (during hardening namely 1070, 1040, 1010 and 980ºC was studied followed by tempering process at 540ºC . It was found that there was a direct relation between the micro hardness magnitude and the austenite temperature, the maximum was 66.1% that achieved at 1070ºC. This finding was significant because there is a great enhancement in the ability of D2 alloy steel to sustain high torsion loads, where the maximum was 191.1% that achieved at 1070ºC.

Some coupled 1D-2D hydrodynamic and water quality models depicting tidal water bodies with complex topography were presented. For the coupled models, finite element method was used to solve the governing equations so as to study tidal rivers with complex topography. Since the 1D and 2D models were coupled, the principle of model coupling was proposed to account appropriately for the factors of water level, flow and pollutant flux and the related dynamical behavior was simulated. Specifically the models were used to probe quantitative pollution contribution of receiving water from neighboring Jiangsu and Zhejiang Provinces to the pollution in the Huangpu River passing through Shanghai City. Numerical examples indicated that the developed coupled 1D-2D models are applicable in tidal river network region of Shanghai.

Lipids in the skin are the most diverse in the entire human body. Their bioactivity in health and disease is underexplored. Prostaglandin D2 has recently been identified as a factor which is elevated in the bald scalp of men with androgenetic alopecia (AGA) and has the capacity to decrease hair lengthening. An enzyme which synthesizes it, prostaglandin D2 synthase (PTGDS or lipocalin-PGDS), is hormone responsive in multiple other organs. PGD2 has two known receptors, GPR44 and PTGDR. GPR44 was found to be necessary for the decrease in hair growth by PGD2 . This creates an exciting opportunity to perhaps create novel treatments for AGA, which inhibit the activity of PTGDS, PGD2 or GPR44. This review discusses the current knowledge surrounding PGD2 , and future steps needed to translate these findings into novel therapies for patients with AGA.

Full Text Available Device-to-device (D2D communications have gained great attentions due to the potential and numerous benefits for cellular networks. However,it also brings tremendous resource allocation challenges for the sake of the constraint of battery life. Up to now, there are limited works attempt to prolong the battery life by improving the energy efficiency (EE. In this paper, we study how to perform resource allocation to increase EE in a interference limited environment under a noncooperative game model. Each D2D pair can reuse all or part of the channel resources allocated to cellular users. An energy-efficient joint power allocation and channel selection is proposed by employing the nonlinear fractional programming. We obtain the optimal power allocation and channel selection through an iterative algorithm called Dinkelbach method. Finally, the algorithm proposed in this paper is verified by simulation.

We have measured the production of Lyα and Hα fluorescence from atomic H and D resulting from the photodissociation of H2, D2 and HD by linearly-polarized photons with energies between 20 and 65 eV. In this energy range, excited photofragments result primarily from the production of doubly-excited molecular species which promptly autoionize or dissociate into two neutrals. Comparison between the relative cross sections of H2 and D2 and the available theory show only qualitative agreement. We will discuss the various systematic effects which affect this and other types of synchrotron-based measurements in this energy range. Support provided by the NSF (Grant PHY-0653379), DOE (LBNL/ALS) and ANSTO (Access to Major Research Facilities Programme).

In quantum gravity, several approaches have been proposed until now for the quantum description of discrete geometries. These theoretical frameworks include loop quantum gravity, causal dynamical triangulations, causal sets, quantum graphity, and energetic spin networks. Most of these approaches describe discrete spaces as homogeneous network manifolds. Here we define Complex Quantum Network Manifolds (CQNM) describing the evolution of quantum network states, and constructed from growing simplicial complexes of dimension $d$. We show that in $d=2$ CQNM are homogeneous networks while for $d>2$ they are scale-free i.e. they are characterized by large inhomogeneities of degrees like most complex networks. From the self-organized evolution of CQNM quantum statistics emerge spontaneously. Here we define the generalized degrees associated with the $\\delta$-faces of the $d$-dimensional CQNMs, and we show that the statistics of these generalized degrees can either follow Fermi-Dirac, Boltzmann or Bose-Einstein distri...

We study the quantum molecular sieving of H2 and D2 through two nanotubes placed end-to-end. An analytic treatment, assuming that the particles have classical motion along the axis of the nanotube and are confined in a potential well in the radial direction, is considered. Using this idealistic model, and under certain conditions, it is found that this device can act as a complete sieve, allowing chemically pure deuterium to be isolated from an isotope mixture. We also consider a more realistic model of two carbon nanotubes and carry out molecular dynamics simulations using a Feynman—Hibbs potential to model the quantum effects on the dynamics of H2 and D2. Sieving is also observed in this case, but is caused by a different process.

Using the concept of a 3-Lie bialgebra, which has recently been defined in arXiv:1604.04475, we construct a Bagger-Lambert-Gustavson (BLG) model for the M2-brane on a Manin triple of a special 3-Lie bialgebra. Then by using the correspondence and the relation between those 3-Lie bialgebra with Lie bialgebra, we reduce this model to an N = (4,4) WZW model (D2-brane), such that its algebraic structure is a Lie bialgebra with one 2-cocycle. In this manner by using the correspondence of the 3-Lie bialgebra and Lie bialgebra (for this special 3-Lie algebra) one can construct the M2-brane from a D2-brane and vice versa. (orig.)

Endovascular treatment of cerebral aneurysms and arteriovenous malformations (AVM) involves navigation of a catheter through the femoral artery and vascular system to the site of pathology. Intra-interventional navigation is done under the guidance of one or at most two two-dimensional (2D) X-ray fluoroscopic images or 2D digital subtracted angiograms (DSA). Due to the projective nature of 2D images, the interventionist needs to mentally reconstruct the position of the catheter in respect to the three-dimensional (3D) patient vasculature, which is not a trivial task. By 3D-2D registration of pre-interventional 3D images like CTA, MRA or 3D-DSA and intra-interventional 2D images, intra-interventional tools such as catheters can be visualized on the 3D model of patient vasculature, allowing easier and faster navigation. Such a navigation may consequently lead to the reduction of total ionizing dose and delivered contrast medium. In the past, development and evaluation of 3D-2D registration methods for endovascular treatments received considerable attention. The main drawback of these methods is that they have to be initialized rather close to the correct position as they mostly have a rather small capture range. In this paper, a novel registration method that has a higher capture range and success rate is proposed. The proposed method and a state-of-the-art method were tested and evaluated on synthetic and clinical 3D-2D image-pairs. The results on both databases indicate that although the proposed method was slightly less accurate, it significantly outperformed the state-of-the-art 3D-2D registration method in terms of robustness measured by capture range and success rate.

Full Text Available Sirish Kondabolu, Rishimani Adsumelli, Joy Schabel, Peter Glass, Srinivas PentyalaDepartment of Anesthesiology, School of Medicine, Stony Brook Medical Center, Stony Brook, New York, USABackground: It is accepted that there is a severe risk of dural puncture in epidural anesthesia. Of major concern to anesthesiologists is unintentional spinal block. Reliable identification of cerebrospinal fluid (CSF from the aspirate is crucial for safe epidural anesthesia. The aim of this study was to determine whether prostaglandin D2 could be clinically used as a marker for the detection of CSF traces.Methods: After obtaining Institutional Review Board approval and patient consent, CSF was obtained from patients undergoing spinal anesthesia, and blood, urine, and saliva were obtained from normal subjects and analyzed for prostaglandin D2 (PGD. CSF (n=5 samples were diluted with local anesthetic (bupivacaine, normal saline and blood in the ratios of 1:5 and 1:10. PGD levels in the CSF samples were analyzed with a PGD-Methoxime (MOX EIA Kit (Cayman Chemicals, MI. This assay is based on the conversion of PGD to a stable derivative, which is analyzed with antiserum specific for PGD-MOX. Results: Different concentrations of pure PGD-MOX conjugate were analyzed by EIA and a standard curve was derived. PGD levels in CSF and CSF with diluents were determined and the values were extrapolated onto the standard curve. Our results show a well-defined correlation for the presence of PGD both in straight CSF samples and in diluted CSF (dilution factor of 1:5 and 1:10. Conclusion: Prostaglandin D2 was reliably identified in CSF by enzyme-linked immunosorbent assay when diluted with local anesthetic, saline, and serum, and can be used as a marker to identify the presence of CSF in epidural aspirates.Keywords: epidural, cerebrospinal fluid, leak, marker, prostaglandin D2

The lifetime of the metastable 5d$^2$D$_{5/2}$ state has been measured for a single trapped Ba$^+$ ion in a Paul trap in Ultra High Vacuum (UHV) in the 10$^{-10}$ mbar pressure range. A total of 5046 individual periods when the ion was shelved in this state have been recorded. A preliminary value $\\tau_{D_{5/2}} = 26.4(1.7)$~s is obtained through extrapolation to zero residual gas pressure.

The lifetime of the metastable 5d ^2D 5/2 state has been measured for a single trapped Ba^+ ion in a Paul trap in Ultra High Vacuum (UHV) in the 10 ^−10 mbar pressure range. A total of 5046 individual periods when the ion was shelved in this state have been recorded. A preliminary value T D 5/2 = 26

We have studied the dissciative ionization of H2 and D2 by electron impact. It is found that in the vicinity of the 2Σ+g dissociation threshold of H+2 (18.08 eV) a significant fraction of the produced protons originates from the process e + H2 → H− + H+ + e (threshold at 17.34 eV). Similar results

Device-to-device (D2D) communications underlying the cellular infrastructure are a technology that have been proposed recently as a promising solution to enhance cellular network capabilities. It improves spectrum utilization, overall throughput, and energy efficiency while enabling new peer-to-peer and location-based applications and services. However, interference is the major challenge, since the same resources are shared by both systems. Therefore, interference management techniques are required to keep the interference under control. In this paper, in order to mitigate interference, we consider centralized and distributed power control algorithms in a one-cell random network model. Existing results on D2D underlay networks assume perfect channel state information (CSI). This assumption is usually unrealistic in practice due to the dynamic nature of wireless channels. Thus, it is of great interest to study and evaluate achievable performances under channel uncertainty. Differently from previous works, we are assuming that the CSI may be imperfect and include estimation errors. In the centralized approach, we derive the optimal powers that maximize the coverage probability and the rate of the cellular user while scheduling as many D2D links as possible. These powers are computed at the base station (BS) and then delivered to the users, and hence the name “centralized”. For the distributed method, the ON–OFF power control and the truncated channel inversion are proposed. Expressions of coverage probabilities are established in the function of D2D links intensity, pathloss exponent, and estimation error variance. Results show the important influence of CSI error on achievable performances and thus how crucial it is to consider it while designing networks and evaluating performances.

The striatum contains a high density of histamine H3 receptors, but their role in striatal function is poorly understood. Previous studies have demonstrated antagonistic interactions between striatal H3 and dopamine D1 receptors at the biochemical level, while contradictory results have been reported about interactions between striatal H3 and dopamine D2 receptors. In the present study, by using reserpinized mice, we demonstrate the existence of behaviorally significant antagonistic postsynap...

Dopamine (DA) is a neurotransmitter with an important influence on learning and memory, which is thought to be due to its modulatory effect on plasticity at central synapses, which in turn depends on activation of D1 and D2 receptors. Methods of brain stimulation (transcranial direct current stimulation, tDCS; paired associative stimulation, PAS) lead to after-effects on cortical excitability that are thought to resemble long-term potentization (LTP)/long-term depression (LTD) in reduced preparations. In a previous study we found that block of D2 receptors abolished plasticity induced by tDCS but had no effect on the facilitatory plasticity induced by PAS. We postulated that the different effect of D2 receptor block on tDCS- and PAS-induced plasticity may be due to the different focality and associativity of the stimulation techniques. However, alternative explanations for this difference could not be ruled out. tDCS also differs from PAS in other aspects, as tDCS induces plasticity by subthreshold neuronal activation, modulating spontaneous activity, whereas PAS induces plasticity via phasic suprathreshold stimulation. The present study in 12 volunteers examined effects of D2 receptor blockade (sulpiride (SULP) 400 mg), on the LTP/LTD-like effects of theta burst transcranial magnetic stimulation (TBS), which has less restricted effects on cortical synapses than that of PAS, and does not induce associative plasticity, similar to tDCS, but on the other hand induces cortical excitability shifts by suprathreshold (rhythmic) activation of cortical neurons similarly to PAS. Administration of SULP blocked both the excitatory and inhibitory effects of intermittent (iTBS) and continuous TBS (cTBS), respectively. As the reduced response to TBS following SULP resembles its effect on tDCS, the results support an effect of DA on plasticity, which might be related to the focality and associativity of the plasticity induced.

Recently, cellular networks are severely overloaded by social-based services, such as YouTube, Facebook and Twitter, in which thousands of clients subscribe a common content provider (e.g., a popular singer) and download his/her content updates all the time. Offloading such traffic through complementary networks, such as a delay tolerant network formed by device-to-device (D2D) communications between mobile subscribers, is a promising solution to reduce the cellular burdens. In the existing s...

Fourier transform spectrometry (FTS) is presently used to record the spontaneous incoherent laser Raman spectra of gases. The high resolution, sensitivity, calibration accuracy and spectral coverage achieved demonstrate the viability of FTS for Raman spectroscopy. Attention is given to the coefficients obtained by fitting measurements obtained from the spectrum of D2, containing both v = 0-0 and 1-0 transitions, to the Dunham (1932) expansion of the vibration-rotation energy levels.

Introduction: Spreading depression (SD) is a propagating wave of depolarization followed by depression of the neuroglial activities and can modulate extracellular dopamine concentrations in the neocortex. It has been shown that the dopaminergic system plays a role in migraine. SD has been suggested as a critical phenomenon in the pathophysiology of migraine. The aim of this study was to investigate the effect of dopamine D2 receptors on the characteristic features of SD in rat neocortical tis...

to variations in the hydrogen-ion concentration in both solvents in the range between 2 x 10 -2 and 2 x 10 -5 M. The acidity determinations involve standardization and storage of the glass electrode in solutions in HzO and subsequent drying of the glass electrode with mercury before immersing it in the 0.5-ml...... the point of view of extrapolating rate data obtained in HzO-DzO mixtures to pure D2O....

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity.

We calculate the annihilation decay rates of the 3D2(2--) and 3D 3(3--) charmonia and bottomonia by using the instantaneous Bethe-Salpeter (BS) method. The wave functions of states with quantum numbers JPC = 2-- and 3-- are constructed. By solving the corresponding instantaneous BS equations, we obtain the mass spectra and wave functions of the quarkonia. The annihilation amplitude is written within Mandelstam formalism and the relativistic corrections are taken into account properly. This is important, especially for high excited states, since their relativistic corrections are large. The results for the 3g channel are as follows: Γ13D2(cc¯)→ggg = 9.24 keV, Γ13D3(cc¯)→ggg = 25.0 keV, Γ13D2(bb¯)→ggg = 1.87 keV and Γ13D3(bb¯)→ggg = 0.815 keV.

Recycling processes for the recovery of metallic content from the electronic wastes are environmentally friendly and economical. This paper reports a method for the recovery and separation of Ni and Co from the sulfate solution by the use of D2EHPA. In this regard, the influence of citrate ion, as a carboxylate ligand, was examined in the separation conditions of Ni and Co via D2EHPA (a poor selective extractant for Ni and Co separation). It was found that the Δ {pH}_{0.5}^{Ni-Co} (the difference between pH values corresponding to 50 pct extraction of metallic ion) increases to 1.5 at the citrate concentration of 0.05 M; this Δ {pH}_{0.5}^{Ni-Co} value is much higher than that obtained in the absence of citrate ion (0.1). Fourier Transform Infrared Spectroscopy (FT-IR) indicated that the citrate ion is co-absorbed during the metallic ions absorption by D2EHPA meaning that the metal-organic complexes contain Co/Ni and citrate ion. Also, the stoichiometric coefficients of the Ni and Co extraction reaction were proposed by applying the slope analysis method.

The crystal structures of the title compounds have been solved by direct methods from single crystal X-ray diffraction. Cisapride: monoclinic, space group P2 1/ n with a=34.210(4), b=7.642(2), c=9.435(1) Å, β=90.93(1)°, Z=4, final R factor=0.044 for 1178 observed reflections. R53757: monoclinic, space group P2 1/ n with a=28.896(3), b=8.054(2), c=10.957(2) Å, β=91.79(1)°, Z=4, final R factor=0.032 for 933 observed reflections. Cisapride, a non-dopamine blocking gastrokinetic, and its closely related analog, R53757, are compared to two very potent D2 antagonists, tropapride and R48788. The analysis of the X-ray determined structures completed by theoretical conformational studies suggests that the structural requirements for all compounds studied seem to be very similar. As shown by PCILO calculations, the presence of a methoxy group on the cisapride piperidine ring does not prevent an optimal orientation of the three putative pharmacophoric elements described for the D2 receptor. Only the nature of the nitrogen lateral chain differs between the D2 antagonists and cisapride.

The precise mechanisms underlying how emotions change breathing patterns remain unclear, but dopamine is a candidate neurotransmitter in the process of emotion-associated breathing. We investigated whether basal dopamine release occurs in the basolateral amygdala (BLA), where sensory-related inputs are received and lead to fear or anxiety responses, and whether D1- and D2-like receptor antagonists affect breathing patterns and dopamine release in the BLA. Adult male mice (C57BL/6N) were perfused with artificial cerebrospinal fluid, a D1-like receptor antagonist (SCH 23390), or a D2-like receptor antagonist ((S)-(-)-sulpiride) through a microdialysis probe in the BLA. Respiratory variables were measured using a double-chamber plethysmograph. Dopamine release was measured by an HPLC. Perfusion of (S)-(-)-sulpiride in the BLA, not SCH 23390, specifically decreased respiratory rate without changes in local release of dopamine. These results suggest that basal dopamine release in the BLA, at least partially, increases respiratory rates only through post-synaptic D2-like receptors, not autoreceptors, which might be associated with emotional responses.

Device-to-Device (D2D) communication is envisioned to play a key role in 5G networks as a technique for meeting the demand for high data rates. In a cellular network, D2D allows not only direct communication between users, but also device relaying. In this paper, a simple instance of device-relaying is investigated, and its impact on fairness among users is studied. Namely, a cellular network consisting of two D2D-enabled users and a base-station (BS) is considered. Thus, the users who want to establish communication with the BS can act as relays for each other’s signals. While this problem is traditionally considered in the literature as a multiple-access channel with cooperation in the uplink, and a broadcast channel with cooperation in the downlink, we propose a different treatment of the problem as a multi-way channel. A simple communication scheme is proposed, and is shown to achieve significant gain in terms of fairness (measured by the symmetric rate supported) in comparison to the aforementioned traditional treatment.

From the analysis for various mobile robots competed in DARPA Robotics Challenge, there are some drawbacks in using two or four legs because bipedal locomotion is not yet suitable for maintaining stability and quadrupedal locomotion is difficult to go through narrow aisles. Motivated by the above observations, we propose a K-R2D2 robot platform with three legs arranged in the form of a triangle like as R2-D2 robot which is a fictional robot character in the Star Wars movies. This robot has 3 legs with tracks in each sole of the leg. It is statically stable since there are three contact points to ground. In addition, three legs are also possible to design a structure walking stairs that can expand and contract in the vertical direction. This paper has presented the conceptual design, it is developed on the purpose of quick response instead of emergent workers to the extreme conditions disasters. This robot is emergency response robot platform KR2D2 with three legs, which is statically stable to walk or wheel depending on the terrains and move quickly as possible as on uneven terrain or stairs.

The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers. PMID:25763838

Full Text Available The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK. This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.

An extensive survey of the D2 absorption spectrum has been performed with the high-resolution VUV Fourier-transform spectrometer of the DESIRS beamline at the SOLEIL synchrotron. The frequency range of 90 000-119 000 cm-1 covers the full depth of the potential wells of the B 1{\\Sigma}+u, B' 1{\\Sigma}+u, and C 1{\\Pi}u electronic states up to the D(1s) + D(2\\ell) dissociation limit. Improved level energies of rovibrational levels have been determined up to respectively v = 51, v = 13, and v = 20. Highest resolution is achieved by probing absorption in a molecular gas jet with slit geometry, as well as in a liquid helium cooled static gas cell, resulting in line widths of ~0.35 cm-1. Extended calibration methods are employed to extract line positions of D2 lines at absolute accuracies of 0.03 cm-1. The D1{\\Pi}u and B" 1{\\Sigma}+u electronic states correlate with the D(1s) + D(3\\ell) dissociation limit, but support a few vibrational levels below the second dissociation limit, respectively v = 0-3 and v = 0-1, and...

Results of a comparative study of the effects of chronic administration of the D2-receptor agonist quinperole (0.1 mg/kg, i.p.) and the D2-receptor antagonist sulpiride (10.0 mg/kg, i.p.) for 14 days on anxiety- and depressive-like behavior in key phases of the ovarian cycle in adult female rats are presented. The model of depression in rats was implemented in Porsolt test, while the anxiety level was assessed in the elevated plus maze test. It is established that the chronic administration of quinperole produced an anxiolytic action in female rats during diesrous, estrous and proestrous phases, but failed to modify depression-like behavior during the entire ovarian cycle. Sulpiride administration resulted in anxiogenic effect in all phases of the ovarian cycle. It was also found that sulpiride produced some modulation of depression-like behavior in connection to ovarian cycle phases, which was a prodepressive action at a moderate level of estrogens and an antidepressant effect at a reduced/enhanced level of estrogen. It is suggested that the extent of involvement of D2-receptors in the mechanisms of anxiety-depressive-like behavior can vary depending on alterations of the hormonal balance during the ovarian cycle. The data obtained are indicative of a close interaction between ovarian hormonal and dopaminergic systems of the brain involved in the mechanisms of anxiety and depression.

The experimental determination of the structure of protein complexes cannot keep pace with the generation of interactomic data, hence resulting in an ever-expanding gap. As the structural details of protein complexes are central to a full understanding of the function and dynamics of the cell machinery, alternative strategies are needed to circumvent the bottleneck in structure determination. Computational protein docking is a valid and valuable approach to model the structure of protein complexes. In this work, we describe a novel computational strategy to predict the structure of protein complexes based on data-driven docking: VORFFIP-driven dock (V-D2OCK). This new approach makes use of our newly described method to predict functional sites in protein structures, VORFFIP, to define the region to be sampled during docking and structural clustering to reduce the number of models to be examined by users. V-D2OCK has been benchmarked using a validated and diverse set of protein complexes and compared to a state-of-art docking method. The speed and accuracy compared to contemporary tools justifies the potential use of VD2OCK for high-throughput, genome-wide, protein docking. Finally, we have developed a web interface that allows users to browser and visualize V-D2OCK predictions from the convenience of their web-browsers.

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation.Ubiquitin-conjugating enzyme E2 D2 is a protein that is encoded by the UBE2D2 gene. Here, we report a lamprey （LaUBE2D2） gene which contained 441-bp open reading frame （ORF） encoding 147 amino acids with a typical UBC domain. Real-time PCR assay showed that the highest expression of the protein inadult lamprey was in the leukocytes, the lowest expression was in the skin, kidney and liver. The high conservation in amino acid sequence of the LaUBE2D2protein with the UBE2D2s from Homo sapiens, Danio rerio, Oreochromis niloticus and Takifugu rubripes, implied that it had similar function with UBE2D2proteins from other species.

The dopamine D2 receptor (D2R) plays an important part in the human central nervous system and it is considered to be a focal target of antipsychotic agents. It is structurally modeled in active and inactive states, in which homodimerization reaction of the D2R monomers is also applied. The ASP2314 (also known as ACR16) ligand, a D2R stabilizer, is used in tests to evaluate how dimerization and conformational changes may alter the ligand binding space and to provide information on alterations in inhibitory mechanisms upon activation. The administration of the D2R agonist ligand ACR16 [(3)H](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ((+)PHNO) revealed Ki values of 32 nM for the D2(high)R and 52 μM for the D2(low)R. The calculated binding affinities of ACR16 with post processing molecular dynamics (MD) simulations analyses using MM/PBSA for the monomeric and homodimeric forms of the D2(high)R were -9.46 and -8.39 kcal/mol, respectively. The data suggests that the dimerization of the D2R leads negative cooperativity for ACR16 binding. The dimerization reaction of the D2(high)R is energetically favorable by -22.95 kcal/mol. The dimerization reaction structurally and thermodynamically stabilizes the D2(high)R conformation, which may be due to the intermolecular forces formed between the TM4 of each monomer, and the result strongly demonstrates dimerization essential for activation of the D2R.

Full Text Available The prevalence of mutant IDH1 brain tumors has generated significant efforts to understand the role of the mutated enzyme product D-2-hydroxyglutarate (D2HG, an oncometabolite, in tumorigenesis, as well as means to eliminate it. Glymphatic clearance was proposed as a pathway that could be manipulated to accelerate D2HG clearance and dictated the study design that consisted of two cohorts of mice bearing U87/mutant IDH1 intracerebral tumors who underwent two microdialysis – providing D2HG interstitial fluid concentrations - sampling periods of awake and asleep (activate glymphatic clearance in a crossover manner. Glymphatic clearance was found not to have a significant effect on D2HG brain tumor interstitial fluid concentrations that were 126.9 ± 74.8 µM awake and 117.6 ± 98.6 µM asleep. These concentrations, although low relative to total brain tumor concentrations of 6.8 ± 3.6 mM, were considered sufficient to be transported by interstitial fluid and taken up into normal cells to cause deleterious effects. A model of D2HG CNS distribution supported this contention and was further supported by in vitro studies that showed D2HG could interfere with immune cell function. The study provides insight into the compartmental distribution of D2HG in the brain wherein the interstitial fluid serves as a dynamic pathway for D2HG to enter normal cells and contribute to tumorigenesis.

The Raman spectra of cubic LiI·H2O and LiI·D2O have been revised. The spectra reveal only internal and librational modes of H2O (D2O). The isotopic ratios νH/νD, are in the range 1.33-1.78......The Raman spectra of cubic LiI·H2O and LiI·D2O have been revised. The spectra reveal only internal and librational modes of H2O (D2O). The isotopic ratios νH/νD, are in the range 1.33-1.78...

Understanding the molecular triggers of pancreatic β-cell proliferation may facilitate the development of regenerative therapies for diabetes. Genetic studies have demonstrated an important role for cyclin D2 in β-cell proliferation and mass homeostasis, but its specific function in β-cell division and mechanism of regulation remain unclear. Here, we report that cyclin D2 is present at high levels in the nucleus of quiescent β-cells in vivo. The major regulator of cyclin D2 expression is glucose, acting via glycolysis and calcium channels in the β-cell to control cyclin D2 mRNA levels. Furthermore, cyclin D2 mRNA is down-regulated during S-G2-M phases of each β-cell division, via a mechanism that is also affected by glucose metabolism. Thus, glucose metabolism maintains high levels of nuclear cyclin D2 in quiescent β-cells and modulates the down-regulation of cyclin D2 in replicating β-cells. These data challenge the standard model for regulation of cyclin D2 during the cell division cycle and suggest cyclin D2 as a molecular link between glucose levels and β-cell replication. PMID:21521747

Adenosine A2A receptor (A2AR)-dopamine D2 receptor (D2R) heteromers are key modulators of striatal neuronal function. It has been suggested that the psychostimulant effects of caffeine depend on its ability to block an allosteric modulation within the A2AR-D2R heteromer, by which adenosine decreases the affinity and intrinsic efficacy of dopamine at the D2R. We describe novel unsuspected allosteric mechanisms within the heteromer by which not only A2AR agonists, but also A2AR antagonists, decrease the affinity and intrinsic efficacy of D2R agonists and the affinity of D2R antagonists. Strikingly, these allosteric modulations disappear on agonist and antagonist coadministration. This can be explained by a model that considers A2AR-D2R heteromers as heterotetramers, constituted by A2AR and D2R homodimers, as demonstrated by experiments with bioluminescence resonance energy transfer and bimolecular fluorescence and bioluminescence complementation. As predicted by the model, high concentrations of A2AR antagonists behaved as A2AR agonists and decreased D2R function in the brain.

The binding properties of the substituted benzamide raclopride to dopamine D2 receptors were studied with membrane preparations from rat and rabbit neostriatum. An analysis of the association kinetics suggested a single binding site but the data from the dissociation experiments were better described by a two-site model. Examination of saturation curves at equilibrium revealed a single class of binding sites in the neostriatum from both species (rat: maximum binding capacity (Bmax) = 247 fmol/mg of protein; rabbit: Bmax = 337 fmol/mg of protein). In cortical regions known to possess a distinct dopaminergic innervation (piriform-entorhinal areas and cingulate cortex) the Bmax values ranged between 9 and 22 fmol/mg of protein. ({sup 3}H)Raclopride binding sites (less than 12 fmol/mg of protein) were also detectable in the dorsal and ventral hippocampus as well as in the somatosensory and visual cortices. The selectivity in the neostriatum was examined by competition experiments with dopaminergic drugs. The rank of potency of agonists and antagonists to displace ({sup 3}H)raclopride binding revealed its selectivity for the dopamine D2 receptor and was essentially the same for both species. Antagonist competition curves could be fitted to a single site but inhibition by agonists was better described assuming a two-site model. The stereospecificity of binding was demonstrated by the use of the enantiomer pairs. These results validate the utilization of the novel benzamide ({sup 3}H)raclopride as a selective marker of dopamine D2 receptors.

Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine's role in attention processing. Here we test the hypotheses that D2/D3 receptors (D2/D3R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D2/D3, SD would disrupt these associations. We measured striatal D2/D3R using positron emission tomography with [11C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D2/D3R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D2/D3R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D2/D3R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D2/D3R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D2/D3R in dorsal striatum counterbalanced the stimulatory influence of D2/D3R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D2/D3R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum. PMID:27219347

The D or L form of 2-hydroxyglutarate (2HG) accumulates in certain rare neurometabolic disorders, and high D-2-hydroxyglutarate (D-2HG) levels are also found in several types of cancer. Although 2HG has been detected in Saccharomyces cerevisiae, its metabolism in yeast has remained largely unexplored. Here, we show that S. cerevisiae actively forms the D enantiomer of 2HG. Accordingly, the S. cerevisiae genome encodes two homologs of the human D-2HG dehydrogenase: Dld2, which, as its human homolog, is a mitochondrial protein, and the cytosolic protein Dld3. Intriguingly, we found that a dld3Δ knock-out strain accumulates millimolar levels of D-2HG, whereas a dld2Δ knock-out strain displayed only very moderate increases in D-2HG. Recombinant Dld2 and Dld3, both currently annotated as D-lactate dehydrogenases, efficiently oxidized D-2HG to α-ketoglutarate. Depletion of D-lactate levels in the dld3Δ, but not in the dld2Δ mutant, led to the discovery of a new type of enzymatic activity, carried by Dld3, to convert D-2HG to α-ketoglutarate, namely an FAD-dependent transhydrogenase activity using pyruvate as a hydrogen acceptor. We also provide evidence that Ser3 and Ser33, which are primarily known for oxidizing 3-phosphoglycerate in the main serine biosynthesis pathway, in addition reduce α-ketoglutarate to D-2HG using NADH and represent major intracellular sources of D-2HG in yeast. Based on our observations, we propose that D-2HG is mainly formed and degraded in the cytosol of S. cerevisiae cells in a process that couples D-2HG metabolism to the shuttling of reducing equivalents from cytosolic NADH to the mitochondrial respiratory chain via the D-lactate dehydrogenase Dld1.

Endovascular treatment of cerebral aneurysms and arteriovenous malformations (AVM) involves navigation of a catheter through the femoral artery and vascular system into the brain and into the aneurysm or AVM. Intra-interventional navigation utilizes digital subtraction angiography (DSA) to visualize vascular structures and X-ray fluoroscopy to localize the endovascular components. Due to the two-dimensional (2D) nature of the intra-interventional images, navigation through a complex three-dimensional (3D) structure is a demanding task. Registration of pre-interventional MRA, CTA, or 3D-DSA images and intra-interventional 2D DSA images can greatly enhance visualization and navigation. As a consequence of better navigation in 3D, the amount of required contrast medium and absorbed dose could be significantly reduced. In the past, development and evaluation of 3D-2D registration methods received considerable attention. Several validation image databases and evaluation criteria were created and made publicly available in the past. However, applications of 3D-2D registration methods to cerebral angiograms and their validation are rather scarce. In this paper, the 3D-2D robust gradient reconstruction-based (RGRB) registration algorithm is applied to CTA and DSA images and analyzed. For the evaluation purposes five image datasets, each comprised of a 3D CTA and several 2D DSA-like digitally reconstructed radiographs (DRRs) generated from the CTA, with accurate gold standard registrations were created. A total of 4000 registrations on these five datasets resulted in mean mTRE values between 0.07 and 0.59 mm, capture ranges between 6 and 11 mm and success rates between 61 and 88% using a failure threshold of 2 mm.

Full Text Available Background. Cerebral ischemia is known to produce brain damage and related behavioural deficits, including memory deficits and motor disorders. Evidence shows that EA significantly promotes recovery of neurological function and thus improves quality of life. Objective. Evidence exists for the involvement of catecholamines in human neuroplasticity. A better understanding of dopaminergic (DAergic modulation in this process will be important. Methods. A total of 72 adult male Sprague-Dawley (SD rats were divided into 6 groups: normal, model, EA, spiperone group, EA + spiperone group, and pergolide. The middle cerebral artery occlusion (MCAO model was used in all 6 groups except the normal group. A behavioural assessment was conducted at 1, 3, 5, and 7 days after MCAO. The percent of brain infarct area was also determined 7 days after MCAO. Tyrosine hydroxylase (TH and growth-associated protein 43 (GAP-43 fluorescence double labeling was performed in the striatum. Results. In this study, we found that EA at Fengchi (GB20 acupoints resulted in marked improvements based on a behavioural assessment. Both TTC staining and GAP-43 immunofluorescence labeling results showed that EA treatment reduced ischemia injury and promoted neuroplasticity compared with the model group. The D2R-selective agonist, pergolide, showed similar results, but these results were reversed by the D2R-selective antagonist, spiperone. We also found that there were more colocalization and expression of GAP-43 and TH in the EA and pergolide groups than those in the other groups. Conclusion. These results suggest that the neuroplasticity induced by EA was mediated by D2 autoreceptors in DAergic neurons.

Fifth Generation (5G) wireless systems are expected to connect an avalanche of “smart” objects disseminated from the largest “Smart City” to the smallest “Smart Home”. In this vision, Long Term Evolution-Advanced (LTE-A) is deemed to play a fundamental role in the Internet of Things (IoT) arena providing a large coherent infrastructure and a wide wireless connectivity to the devices. However, since LTE-A was originally designed to support high data rates and large data size, novel solutions are required to enable an efficient use of radio resources to convey small data packets typically exchanged by IoT applications in “smart” environments. On the other hand, the typically high energy consumption required by cellular communications is a serious obstacle to large scale IoT deployments under cellular connectivity as in the case of Smart City scenarios. Network-assisted Device-to-Device (D2D) communications are considered as a viable solution to reduce the energy consumption for the devices. The particular approach presented in this paper consists in appointing one of the IoT smart devices as a collector of all data from a cluster of objects using D2D links, thus acting as an aggregator toward the eNodeB. By smartly adapting the Modulation and Coding Scheme (MCS) on the communication links, we will show it is possible to maximize the radio resource utilization as a function of the total amount of data to be sent. A further benefit that we will highlight is the possibility to reduce the transmission power when a more robust MCS is adopted. A comprehensive performance evaluation in a wide set of scenarios will testify the achievable gains in terms of energy efficiency and resource utilization in the envisaged D2D-based IoT data collection. PMID:27338385

Full Text Available Fifth Generation (5G wireless systems are expected to connect an avalanche of “smart” objects disseminated from the largest “Smart City” to the smallest “Smart Home”. In this vision, Long Term Evolution-Advanced (LTE-A is deemed to play a fundamental role in the Internet of Things (IoT arena providing a large coherent infrastructure and a wide wireless connectivity to the devices. However, since LTE-A was originally designed to support high data rates and large data size, novel solutions are required to enable an efficient use of radio resources to convey small data packets typically exchanged by IoT applications in “smart” environments. On the other hand, the typically high energy consumption required by cellular communications is a serious obstacle to large scale IoT deployments under cellular connectivity as in the case of Smart City scenarios. Network-assisted Device-to-Device (D2D communications are considered as a viable solution to reduce the energy consumption for the devices. The particular approach presented in this paper consists in appointing one of the IoT smart devices as a collector of all data from a cluster of objects using D2D links, thus acting as an aggregator toward the eNodeB. By smartly adapting the Modulation and Coding Scheme (MCS on the communication links, we will show it is possible to maximize the radio resource utilization as a function of the total amount of data to be sent. A further benefit that we will highlight is the possibility to reduce the transmission power when a more robust MCS is adopted. A comprehensive performance evaluation in a wide set of scenarios will testify the achievable gains in terms of energy efficiency and resource utilization in the envisaged D2D-based IoT data collection.

Full Text Available Whereas positron emission tomography (PET with the antagonist ligand [18F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [18F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d., and again at a later date, after withholding pramipexole 48–72 h (OFF-Sifrol; in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01 occupancy at [18F]fallypride binding sites in globus pallidus (8% thalamus (9% and substantia nigra (19%, as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum.

Fifth Generation (5G) wireless systems are expected to connect an avalanche of "smart" objects disseminated from the largest "Smart City" to the smallest "Smart Home". In this vision, Long Term Evolution-Advanced (LTE-A) is deemed to play a fundamental role in the Internet of Things (IoT) arena providing a large coherent infrastructure and a wide wireless connectivity to the devices. However, since LTE-A was originally designed to support high data rates and large data size, novel solutions are required to enable an efficient use of radio resources to convey small data packets typically exchanged by IoT applications in "smart" environments. On the other hand, the typically high energy consumption required by cellular communications is a serious obstacle to large scale IoT deployments under cellular connectivity as in the case of Smart City scenarios. Network-assisted Device-to-Device (D2D) communications are considered as a viable solution to reduce the energy consumption for the devices. The particular approach presented in this paper consists in appointing one of the IoT smart devices as a collector of all data from a cluster of objects using D2D links, thus acting as an aggregator toward the eNodeB. By smartly adapting the Modulation and Coding Scheme (MCS) on the communication links, we will show it is possible to maximize the radio resource utilization as a function of the total amount of data to be sent. A further benefit that we will highlight is the possibility to reduce the transmission power when a more robust MCS is adopted. A comprehensive performance evaluation in a wide set of scenarios will testify the achievable gains in terms of energy efficiency and resource utilization in the envisaged D2D-based IoT data collection.

Whereas positron emission tomography (PET) with the antagonist ligand [(18)F]fallypride reveals the composite of dopamine D2 and D3 receptors in brain, treatment of Parkinson's disease (PD) patients with the D3-prefering agonist pramipexole should result in preferential occupancy in the nucleus accumbens, where the D3-subtype is most abundant. To test this prediction we obtained pairs of [(18)F]fallypride PET recordings in a group of nine PD patients, first in a condition of treatment as usual with pramipexole (ON-Sifrol; 3 × 0.7 mg p.d.), and again at a later date, after withholding pramipexole 48-72 h (OFF-Sifrol); in that condition the serum pramipexole concentration had declined by 90% and prolactin levels had increased four-fold, in conjunction with a small but significant worsening of PD motor symptoms. Exploratory comparison with historical control material showed 14% higher dopamine D2/3 availability in the more-affected putamen of patients OFF medication. On-Sifrol there was significant (p ˂ 0.01) occupancy at [(18)F]fallypride binding sites in globus pallidus (8%) thalamus (9%) and substantia nigra (19%), as well as marginally significant occupancy in frontal and temporal cortex of patients. Contrary to expectation, comparison of ON- and OFF-Sifrol results did not reveal any discernible occupancy in nucleus accumbens, or elsewhere in the extended striatum; present methods should be sensitive to a 10% change in dopamine D2/3 receptor availability in striatum; the significant findings elsewhere in the basal ganglia and in cerebral cortex are consistent with a predominance of D3 receptors in those structures, especially in substantia nigra, and imply that therapeutic effects of pramipexole may be obtained at sites outside the extended striatum.

Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety voluntee...

of carrageenan in the presence of gel-promoting counterions. The aggregates do not disappear at 60 degrees C, although at this temperature the molecules should partially lose their ordered conformation. The network formation, observed by SANS, does not happen in high-contrast system immediately after cooling......SANS of Na+-iota-carrageenan in D2O/saline solutions was measured as a function of concentration, temperature and type of counterions (K+ or Na+). High and low scattering-contrasted gels and solutions were detected. High contrast is caused by aggregation of low-hydrated chains at high concentration...

Kinetic model of hypophosphite oxidation on a nickel electrode was studied in D2Osolution in order to reach a better understanding of the oxidation mechanism. In the model the electrooxidation of hypophosphite undergo a H abstraction of hypophosphite from the P-H bond to form the phosphorus-centered radical PHO2-, which subsequently is electrochemically reacted with water to form the final product, phosphite. The kinetic equations were derived, and the kinetic parameters were obtained from a comparison of experimental results and the kinetic equations. The process of hypophosphite electrooxidation could be well simulated by this model

A cryogenic loading system for introducing H2 and D2 into the diamond anvil cell has been designed and constructed. The integration of pressure loading mechanism, ruby fluorescence spectrometer, and microscope camera allows for in situ tuning and calibrating the pressure. The performance of the system has been demonstrated by successful synthesis of hydride and deuteride of transition metal and rare earth metal. Our cryogenic methodology features facile start-over of loading and in situ electrical resistance measurement of as-synthesized sample.

In the (qq) quark model, the states π2(1670) and η2(1645) are assigned as the 11D2 meson nonet. The partner of state η2 (1645) needs further confirmation in the experiments. We employ the meson-meson mixing and the Regge trajectory methods to calculate the mass of the partner of state η2 (1645) to be 1879.8 MeV and 1863 ± 24 MeV respectively. We also calculate the strong decay width in the 3Po decay model. These predictions can be compared with experiments in the future.

The main challenge for any manufacturer is to achieve higher quality of their final products with maintains minimum machining time. In this research final surface roughness analysed and optimized with maximum 0.3 mm flank wear length. The experiment was investigated the effect of cutting speed, feed rate and depth of cut on the final surface roughness using D2 as a work piece hardened to 52-56 HRC, and coated carbide as cutting tool with higher cutting speed 120-240 mm/min. The experiment has been conducted using L9 design of Taguchi collection. The results have been analysed using JMP software.

Dopamine D2 receptor (DRD2) deficiency increases renal inflammation and blood pressure in mice. We show here that long-term renal-selective silencing of Drd2 using siRNA increases renal expression of proinflammatory and profibrotic factors and blood pressure in mice. To determine the effects of renal-selective rescue of Drd2 expression in mice, the renal expression of DRD2 was first silenced using siRNA and 14 days later rescued by retrograde renal infusion of adeno-associated virus (AAV) vec...

The development of the flat moderator concept at ESS recently opened up the possibility that a single flat moderator above the target could serve all the scattering instruments, that rely on high brightness. This would allow for the introduction of a fundamentally different moderator below the target for the complementary needs of certain fundamental physics experiments. To facilitate experiments depending on the total number of neutrons in a sizable beam, the option of a voluminous D2 moderator, in a large cross-section extraction guide is discussed and its neutronic performance is assessed.

The sliding wear and impact wear resistances of D2 steel with nitriding layer, PVD titanium nitride coating and their duplex treatment were investigated. The experimental results suggest that the duplex treatment has the best sliding and impact wear resistances under experimental conditions. And the wear resistance of PVD titanium nitride is better than that of nitriding. The impact wear resistance and wear mechanism of all three surface layers remain unchanged under impact load of 0.2 J or 1 J. All samples end with the same symptom of flaking.

We study modulation-free methods for producing sub-Doppler, dispersive line shapes for laser stabilization near the potassium D2 transitions at 767 nm. Polarization spectroscopy is performed and a comparison is made between the use of a mirror or beam splitter for aligning the counter-propagating pump and probe beams. Conventional magnetically-induced dichroism is found to suffer from a small dispersion and large background offset. We therefore introduce a modified scheme, using two spatially separated pump-probe beam pairs. Finally we compare our results to methods using phase modulation and heterodyne detection.

Using high resolution laser-atomic-beam spectroscopy, Zeeman- and Paschen-Back-effects of the hyperfine structure of the sodium resonance lines were studied in magnetic fields up to 280 Gauss without perturbation by cross-over resonances. The observed behaviour of the components of the D2-line is compared with results of theoretical calculations for the splitting and the relative intensity of each Zeeman-component of the line. Full agreement between theory and experiment can be stated. Additionally, the relative intensities of the components of the D 1-line are given.

Evidence suggests atypical antipsychotic treatment is associated with a lower incidence of tardive dyskinesia (TD) than typical antipsychotic drugs, and is a potential antidyskinetic treatment. We present the case of a middle-aged woman never previously exposed to antipsychotic treatment who developed TD after 6 months of olanzapine monotherapy. Substitution of quetiapine for olanzapine alleviated her TD symptoms. The case demonstrates that atypical antipsychotic drugs have different effects in relation to TD. Potential psychopharmacological mechanisms explaining these differences are discussed, highlighting the importance of D2 receptor occupancy by atypical antipsychotic drugs for TD.

We solve the non-relativistic Coulomb Shrodinger equation in d = 2+1 via sinc collocation. We get excellent convergence using a generalized sinc basis set in position space. Since convergence in position space could not be obtained with more common numerical techniques, this result helps to corroborate the conjecture that the use of a localized basis set within the context of light cone quantization can yield much better convergence. All of the computations presented here were performed on an IBM-compatible PC with an Intel 486DX2-66 microchip.

A kinematically complete measurement of the four-body breakup reaction d+2H-->2ps+2ns --> p +p +n +n has been performed at 15 MeV deuteron beam of the SINP MSU. The two protons and neutron were detected at angles close to those of emission of 2ps and 2ns systems. The energy of singlet dineutron state was determined by comparing experimental TOF spectrum of breakup neutrons with simulated spectra depending on this energy. A low value Enn = 0.076 +/- 0.006 keV obtained by fitting procedure apparently indicates an effective enhancement of nn-interaction in the intermediate state of studied reaction.

Summary Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages. PMID:27559410

The phase diagrams of adsorbed monolayers of D2, H2, O2, and 3He on graphite have been measured by neutron diffraction. H2 and D2-layers have a registered √3 structure at low coverages, and at monolayer completion they have a dense triangular structure, which is incommensurate with the substrate....

Full Text Available Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages.

A mechanism-based PK-PD model was developed to predict the time course of dopamine D-2 receptor occupancy (D2RO) in rat striatum following administration of olanzapine, an atypical antipsychotic drug. A population approach was utilized to quantify both the pharmacokinetics and pharmacodynamics of ol

textabstractIn the present study the distribution of dopamine D2 receptors in rat spinal cord was determined by means of immunocytochemistry using an anti-peptide antibody, directed against the putative third intracellular loop of the D2 receptor and in situ hybridization (ISH) using a [35S]UTP

Dopamine D-2 receptors, similar to other G-protein-coupled receptors, exist in a high- and low-affinity state for agonists. Based upon a review of the methods for detecting D-2 receptor agonist high-affinity states, we discuss alterations of such states in animal models of disease and the implicatio

Full Text Available Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc have beenproposed to contribute to drug-mediated addictive behaviors. Here we have used anoptogenetic approach to examine the role of NAc medium spiny neurons (MSNs expressingdopamine D2 receptors (D2R in cocaine-induced behavioral sensitization. Adeno-associatedviral vectors coding channelrhodopsin-2 (ChR2 were delivered into the NAc of D2R-Cretransgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2RMSNsform local inhibitory circuits, because photostimulation of D2R-MSN evokedinhibitory postsynaptic currents in neighboring MSNs. Photostimulation of NAc D2R-MSNin vivo affected neither the initiation nor the expression of cocaine-induced behavioralsensitization. However, photostimulation during the drug withdrawal period attenuatedexpression of cocaine-induced behavioral sensitization. These results show that D2R-MSNsof NAc play a key role in withdrawal-induced plasticity and may contribute to relapse aftercessation of drug abuse.

Long-lasting, drug-induced adaptations within the nucleus accumbens (NAc) have been proposed to contribute to drug-mediated addictive behaviors. Here we have used an optogenetic approach to examine the role of NAc medium spiny neurons (MSNs) expressing dopamine D2 receptors (D2Rs) in cocaine-induced behavioral sensitization. Adeno-associated viral vectors encoding channelrhodopsin-2 (ChR2) were delivered into the NAc of D2R-Cre transgenic mice. This allowed us to selectively photostimulate D2R-MSNs in NAc. D2R-MSNs form local inhibitory circuits, because photostimulation of D2R-MSN evoked inhibitory postsynaptic currents (IPSCs) in neighboring MSNs. Photostimulation of NAc D2R-MSN in vivo affected neither the initiation nor the expression of cocaine-induced behavioral sensitization. However, photostimulation during the drug withdrawal period attenuated expression of cocaine-induced behavioral sensitization. These results show that D2R-MSNs of NAc play a key role in withdrawal-induced plasticity and may contribute to relapse after cessation of drug abuse.

Surface enhanced Raman scattering (SERS) is generally and widely used to enhance the vibrational fingerprint of molecules located at the vicinity of noble metal nanoparticles. In this work, SERS is originally used to enhance the own vibrational density of states (VDOS) of nude and isolated gold nanoparticles. This offers the opportunity of analyzing finite size effects on the lattice dynamics which remains unattainable with conventional techniques based on neutron or x-ray inelastic scattering. By reducing the size down to few nanometers, the role of surface atoms versus volume atoms become dominant, and the “text-book” 3D-2D transition on the dynamical behavior is experimentally emphasized. “Anomalies” that have been predicted by a large panel of simulations at the atomic scale, are really observed, like the enhancement of the VDOS at low frequencies or the occurrence of localized modes at frequencies beyond the cut-off in bulk. Consequences on the thermodynamic properties at the nanoscale, like the reduction of the Debye temperature or the excess of the specific heat, have been evaluated. Finally the high sensitivity of reminiscent bulk-like phonons on the arrangements at the atomic scale is used to access the morphology and internal disorder of the nanoparticles.

Full Text Available Gotech GT-7010-D2E is a tensile testing machine used in Metallurgical Engineering Laboratory UNTIRTA. The machine are used both for practical and Materials Engineering specimen testing demanded by several industries. The machine can perform tensile tests well, but for the analysis is done manually, so it requires a lot of time and accuracy of the analysis results are not very accurate. Therefore, it’s needed a software that can analyze the results of the tensile test in the form of graphs in real time. Software visualization is created using Visual Basic 6.0 and data from tensile testing machine is stored using Microsoft Access database. The software is designed to record any characters that appear in the LCD on the control panel of a tensile testing machine and then process them to be a graphic. Based on the results of the implementation of the specimen plate and wire observations prove that the difference between the use of visualization software is more accurate and effective in their use of time, compared to manual observation that requires further analysis of the test results. In software visualization results of tensile test, the mechanical properties can be analyzed directly from the test results and graphs of data obtained in real time.

With the development of flexible electronic devices and large-scale energy storage technologies, functional polymer-matrix nanocomposites with high permittivity (high-k) are attracting more attention due to their ease of processing, flexibility, and low cost. The percolation effect is often used to explain the high-k characteristic of polymer composites when the conducting functional fillers are dispersed into polymers, which gives the polymer composite excellent flexibility due to the very low loading of fillers. Carbon nanotubes (CNTs) and graphene nanosheets (GNs), as one-dimensional (1D) and two-dimensional (2D) carbon nanomaterials respectively, have great potential for realizing flexible high-k dielectric nanocomposites. They are becoming more attractive for many fields, owing to their unique and excellent advantages. The progress in dielectric fields by using 1D/2D carbon nanomaterials as functional fillers in polymer composites is introduced, and the methods and mechanisms for improving dielectric properties, breakdown strength and energy storage density of their dielectric nanocomposites are examined. Achieving a uniform dispersion state of carbon nanomaterials and preventing the development of conductive networks in their polymer composites are the two main issues that still need to be solved in dielectric fields for power energy storage. Recent findings, current problems, and future perspectives are summarized.

Phospholipase D2 (PLD2) is an enzyme that produces phosphatidic acid (PA), a lipid messenger molecule involved in a number of cellular events including, through its membrane curvature properties, endocytosis. The PLD2 knock out (PLD2KO) mouse has been previously reported to be protected from insult in a model of Alzheimer's disease. We have further analysed a PLD2KO mouse using mass spectrophotometry of its lipids and found significant differences in PA species throughout its brain. We have examined the expression pattern of PLD2 which allowed us to define which region of the brain to analyse for defect, notably PLD2 was not detected in glial-rich regions. The expression pattern lead us to specifically examine the mitral cells of olfactory bulbs, the Cornus Amonis (CA) regions of the hippocampus and the Purkinje cells of the cerebellum. We find that the change to longer PA species correlates with subtle architectural defect in the cerebellum, exemplified by ectopic Purkinje cells and an adult-onset deficit of olfaction. These observations draw parallels to defects in the reelin heterozygote as well as the effect of high fat diet on olfaction. PMID:27658289

Full Text Available Background: Mushrooms are the only non-animal food source of vitamin D. Wild mushrooms have naturally high vitamin D2 content, and cultivated mushrooms produce vitamin D2 from ergosterol when exposed to supplementary UV-B during the post-harvest phase.Objectives: This study investigated the effects of providing supplementary UV-B during the growth phase on vitamin D2 formation and the interactions with growth of mushrooms, as compared to supplementary UV-B during the post-harvest phase or exposure to sunlight for both cultivated and wild mushrooms.Methods: Experiments were carried out with exposure to supplementary UV-B just prior to harvest in the range of 0–2,400 mJ cm−2. Mushrooms grew for 2 days with or without repeated UV-B exposure each day. Vitamin D2 and growth rate were determined. In addition, some mushrooms were post-harvest treated by exposure at 200 mJ cm−2 supplementary UV-B or natural sunlight, prior to vitamin D2 determination.Results: The content of vitamin D2 was 0.2–164 µg 100 g−1 fresh weight, and there was a linear relationship between UV-dose up to 1,000 mJ cm−2 and vitamin D2 content. The fast growth rate of the mushrooms diluted the vitamin D2 from 24 to 3 µg 100 g−1 within 2 days of exposure at 200 mJ cm−2. Following repeated UV-B exposure, vitamin D2 increased to 33 µg vitamin D2 100 g−1. Growth was unaffected by UV-B. Post-harvest exposure to supplementary UV-B resulted in a higher vitamin D2 content of 32 µg 100 g−1 compared to the 24 µg 100 g−1 obtained from exposure to UV-B during the growth phase. In contrast, wild and cultivated mushrooms with and without exposure to sunlight had vitamin D2 content in the range of 0.2–1.5 µg vitamin D2 100 g−1.Conclusions: This study showed that mushrooms with a well-defined content of vitamin D2 can be obtained by exposure to supplementary UV-B just prior to harvest.

of the striatonigral type (MSA) and healthy subjects. METHODS: SPECT measurements of the dopamine transporter (DAT) were done with 123I-beta-CIT, while for determination of the dopamine D2-like receptors (D2), 123I-epidepride was used. Clinical evaluation and SPECT scans were carried out in 14 patients with IPD, eight...... asymmetry than MSA patients. Striatal D2 binding did not differ significantly between patients and healthy controls but the ratio between caudate DAT and D2 binding was significantly higher in patients with IPD than in those with MSA, even when disease severity was taken into account. CONCLUSION: Patients...... diagnostic information, since the ratio between DAT and D2 receptor binding is significantly higher in IPD than in MSA...

A combined theoretical and experimental study of lithium palladium deuteride (Li2PdD2) subjected to pressures up to 50 GPa reveals one structural phase transition near 10 GPa, detected by synchrotron powder x-ray diffraction, and metadynamics simulations. The ambient-pressure tetragonal phase of Li2PdD2 transforms into a monoclinic C2/m phase that is distinct from all known structures of alkali metal-transition metal hydrides/deuterides. The structure of the high-pressure phase was characterized using ab initio computational techniques and from refinement of the powder x-ray diffraction data. In the high-pressure phase, the PdD2 complexes lose molecular integrity and are fused to extended [PdD2]∞ chains. The discovered phase transition and new structure are relevant to the possible hydrogen storage application of Li2PdD2 and alkali metal-transition metal hydrides in general.

Dysregulated expression and function of dopamine D2 receptors (D2Rs) are implicated in drug addiction, Parkinson's disease and schizophrenia. In the current study, we examined whether D2Rs are modulated by regulator of G protein signaling 2 (RGS2), a member of the RGS family that regulates G protein signaling via acceleration of GTPase activity. Using neuroblastoma 2a (N2A) cells, we found that RGS2 was immunoprecipitated by aluminum fluoride-activated Gαi2 proteins. RGS2 siRNA knockdown enhanced membrane [(35)S] GTPγS binding to activated Gαi/o proteins, augmented inhibition of cAMP accumulation and increased ERK phosphorylation in the presence of a D2/D3R agonist quinpirole when compared to scrambled siRNA treatment. These data suggest that RGS2 is a negative modulator of D2R-mediated Gαi/o signaling. Moreover, RGS2 knockdown slightly increased constitutive D2R internalization and markedly abolished quinpirole-induced D2R internalization assessed by immunocytochemistry. RGS2 knockdown did not compromise agonist-induced β-arrestin membrane recruitment; however, it prevents β-arrestin dissociation from the membrane after prolonged quinpirole treatment during which time β-arrestin moved away from the membrane in control cells. Additionally, confocal microscopy analysis of β-arrestin post-endocytic fate revealed that quinpirole treatment caused β-arrestin to translocate to the early and the recycling endosome in a time-dependent manner in control cells whereas translocation of β-arrestin to these endosomes did not occur in RGS2 knockdown cells. The impaired β-arrestin translocation likely contributed to the abolishment of quinpirole-stimulated D2R internalization in RGS2 knockdown cells. Thus, RGS2 is integral for β-arrestin-mediated D2R internalization. The current study revealed a novel regulation of D2R signaling and internalization by RGS2 proteins.

ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity. We show that the export is dependent on the phosphorylation of two SQ/TQ motifs, suggesting a novel direct interaction between ATM and ADP-ribosylation. Lastly, we show that MacroD2 nuclear export temporally restricts its recruitment to DNA lesions, which may decrease the net ADP-ribosylhydrolase activity at the site of DNA damage. Together, our results identify a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. PMID:28069995

The putamen has a somatotopic organization of neurons identified by correspondence of firing rates with selected body part movements, as well as by complex, but organized, differential cortical projections onto putamen. In isolated focal dystonia, whole putaminal binding of dopamine D2-like receptor radioligands is quantitatively decreased, but it has not been known whether selected parts of the putamen are differentially affected depending upon the body part affected by dystonia. The radioligand [(18)F]spiperone binds predominantly to D2-like receptors in striatum. We hypothesized that the spatial location of [(18)F]spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To address statistical and methodological concerns, we chose a straightforward but robust image analysis method. An automated algorithm located the peak location of [(18)F]spiperone binding within the striatum, relative to a brain atlas, in each of 14 patients with cranial dystonia and 8 patients with hand dystonia. The mean (left and right) |x|, y, and z coordinates of peak striatal binding for each patient were compared between groups by t test. The location of peak [(18)F]spiperone binding within the putamen differed significantly between groups (cranial dystonia zputamen depending on the body part manifesting dystonia.